42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... posthumous child or stepchild of a deceased smallpox vaccine recipient or vaccinia contact who, at the time... vaccinated him/herself. (g) Covered countermeasure means smallpox (vaccinia) vaccines, cidofovir and its...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

42 CFR 102.42 - Deadlines for filing request forms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.42 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) General. Filing deadlines vary depending on whether the injured individual is a smallpox vaccine recipient... this Program. (c) Smallpox vaccine recipients. All Request Forms filed by, or on behalf of, a smallpox...

Emergency physicians' perspectives on smallpox vaccination.

PubMed

Kwon, Nancy; Raven, Maria C; Chiang, William K; Moran, Gregory J; Jui, Jon; Carter, Richard A; Goldfrank, Lewis

2003-06-01

To evaluate emergency physician (EP) attitudes toward smallpox vaccination, the treatment of patients with suspected smallpox, and the threat of a bioterrorist attack. This was a prospective study utilizing a standardized survey instrument that was distributed on November 16, 2002, and collected by February 1, 2003. EPs from a sample of 50 accredited emergency medicine programs were surveyed regarding their perspectives on smallpox vaccination. A total of 989 surveys were collected from 42 emergency medicine programs. Of the respondents, 43.4% would currently volunteer for smallpox vaccination. EPs previously vaccinated against smallpox were 1.46 times more likely to volunteer for vaccination (95% CI = 1.14 to 1.93). EPs who believed they were at risk for complications were less than half as likely to volunteer for vaccination. EPs who perceived a significant risk of a bioterrorist attack were 2.7 times more likely to volunteer for the vaccine compared with those who thought the risk was minimal (95% CI = 2.06 to 3.47). Of the respondents, 34.4% believed the risks of the vaccination outweighed the benefits, 33% did not, and 32.6% were unsure. Currently, fewer than half of EPs surveyed would volunteer for smallpox vaccination. Factors associated with a willingness to be vaccinated include previous smallpox vaccination and the perceived threat of a bioterrorist attack. The variation in EP attitudes toward smallpox vaccination may be due to uncertain risk-to-benefit ratio. The opinions and actions of EPs may be influential on current and future government policy and public opinion.

[The history of smallpox vaccination in the Imperial Moscow foster house].

PubMed

Sher, S A

2011-01-01

The article deals with the history of vaccination against natural smallpox which is directly connected to the Imperial Moscow foster house which became one of smallpox vaccination centers in Russia of XIX century. In 1801, when variolations were substituted by more safe cowpox vaccinations, in Russia the first vaccination using the method of Jenner was made exactly in in the Imperial Moscow foster house. From 1805, the smallpox vaccination received the status of force of law, the Imperial Moscow foster house began to produce and to distribute the smallpox vaccine all over the country and apply the smallpox vaccination not only to its foster children but to all turned to and, besides that, to train the smallpox vaccination. In 1857, the Imperial Moscow foster house became the first establishment in Russia where the revaccination was applied. In 1980, the WHO proclaimed that the implementation of the global program of smallpox irradiation resulted in the natural smallpox elimination on Earth. The smallpox became the first communicable disease defeated due to mass vaccination. One third of Earth population was vaccinated by the Soviet vaccine, which originated mainly because of the activities of physicians of the Imperial Moscow foster house.

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

42 CFR 102.31 - Medical benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.31 Medical benefits. (a) Smallpox vaccine recipients and vaccinia... estate of a deceased smallpox vaccine recipient or vaccinia contact as long as such benefits were accrued...

Smallpox: clinical features, prevention, and management.

PubMed

Guharoy, Roy; Panzik, Robert; Noviasky, John A; Krenzelok, Edward P; Blair, Donald C

2004-03-01

To describe a general overview of smallpox, clinical presentation, diagnosis, adverse events, and management of both pre- and postexposure vaccination. Literature was identified by search of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1966-May 2003) databases using the key terms smallpox, bioterrorism, biological warfare, and smallpox vaccine. Articles identified from data sources were evaluated, and relevant information was included in this review. Smallpox is spread by human-to-human contact with an infected host and therefore can be contagious. The mortality rate for smallpox is approximately 30%. While the disease was completely eradicated by 1980 with successful use of smallpox vaccine, concern has been raised that smallpox may emerge as a tool of bioterrorism. This concern, combined with the reality of current smallpox vaccination programs in the military and selected civilian populations, mandates a clear understanding of vaccination-related adverse events and contraindications by all healthcare professionals. The vaccine may cause moderate to severe adverse events such as eczema vaccinatum, progressive vaccinia, and generalized vaccinia. The balance between the risks and benefits of mass vaccination in prevention of an epidemic is not clear. The Centers for Disease Control and Prevention has established a guideline for appropriate use of smallpox vaccine in the civilian population.

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.30 - Benefits available to different categories of requesters under this program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Available Benefits § 102.30 Benefits... vaccine recipients and vaccinia contacts. A requester who is an eligible smallpox vaccine recipient or... vaccine recipient or vaccinia contact may be entitled to receive a death benefit. (c) Benefits available...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2011 CFR

2011-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2013 CFR

2013-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2014 CFR

2014-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2012 CFR

2012-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.81 - Calculation of benefits for lost employment income.

Code of Federal Regulations, 2010 CFR

2010-10-01

... VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.81 Calculation of benefits... of work lost as a result of a covered injury or its health complications if the smallpox vaccine... based on the smallpox vaccine recipient or vaccinia contact's gross employment income, which includes...

42 CFR 102.50 - Medical records necessary to establish that a covered injury was sustained.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed... to establish that a smallpox vaccine recipient or vaccinia contact sustained a covered injury, a... the smallpox vaccine) or vaccinia contracted through accidental vaccinia inoculation. (c) If certain...

[A study on the 1946 smallpox epidemic in Japan and measures taken against it].

PubMed

Tanaka, Seiji; Sugita, Satoru; Marui, Eiji

2014-09-01

In early 1946, immediately after World War II, there was a smallpox epidemic in Japan. In this paper we investigated trends in the occurrence of smallpox by week and region using official documents of the General Headquarters, Supreme Commander for the Allied Powers (GHQ/SCAP), which are stored in the National Diet Library Modern Japanese Political History Materials Room, and summarized the measures taken against this epidemic. The following two points were clarified: 1) The 1946 smallpox epidemic peaked in Week 13 (March 24-30; 1,405 new patients), and the highest morbidity during this epidemic was seen in Hyogo Prefecture, followed by Osaka Prefecture, Aichi Prefecture, Tokyo Prefecture, and Hokkaido Prefecture. 2) Measures taken against this epidemic were classified into the following three stages: 1. "Vaccine shortage/Manufacture acceleration stage," 2. "Vaccine sufficiency/Smallpox vaccination program implementation stage," and 3. "Detection of defects in vaccination technique/Reimplementation of the smallpox vaccination program stage".

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2012 CFR

2012-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2014 CFR

2014-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2013 CFR

2013-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2011 CFR

2011-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.53 - Documentation a survivor must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be Deemed Eligible... documentation required in: (1) Section 102.51(a)(2)-(4) (documentation requirements for smallpox vaccine recipients), in the case of a deceased smallpox vaccine recipient. The survivor requester may submit a...

42 CFR 102.61 - Documentation an eligible requester seeking benefits for lost employment income must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for... smallpox vaccine recipient or vaccinia contact as a result of the covered injury or its health... had not used paid leave); (b) The smallpox vaccine recipient or vaccinia contact's gross employment...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

42 CFR 102.33 - Death benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM... under this Program if the Secretary determines that an otherwise eligible deceased smallpox vaccine... vaccine recipient or vaccinia contact during his or her lifetime and to his or her estate after death. (c...

SWOT analysis: strengths, weaknesses, opportunities and threats of the Israeli Smallpox Revaccination Program.

PubMed

Huerta, Michael; Balicer, Ran D; Leventhal, Alex

2003-01-01

During September 2002, Israel began its current revaccination program against smallpox, targeting previously vaccinated "first responders" among medical and emergency workers. In order to identify the potential strengths and weaknesses of this program and the conditions under which critical decisions were reached, we conducted a SWOT analysis of the current Israeli revaccination program, designed to identify its intrinsic strengths and weaknesses, as well as opportunities for its success and threats against it. SWOT analysis--a practical tool for the study of public health policy decisions and the social and political contexts in which they are reached--revealed clear and substantial strengths and weaknesses of the current smallpox revaccination program, intrinsic to the vaccine itself. A number of threats were identified that may jeopardize the success of the current program, chief among them the appearance of severe complications of vaccination. Our finding of a lack of a generation of knowledge on smallpox vaccination highlights the need for improved physician education and dissipation of misconceptions that are prevalent in the public today.

42 CFR 102.52 - Documentation a vaccinia contact must submit to be deemed eligible by the Secretary.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation To Be... in § 102.3(x)(1)-(3) (a person meeting the definition of a smallpox vaccine recipient, except for the... individual described in § 102.3(x)(1)-(3) (a person meeting the definition of a smallpox vaccine recipient...

Can smallpox response teams use the experience of disease management programs?

PubMed

Kozma, Chris M

2003-02-01

Any attempt to widely disperse smallpox vaccinations will necessitate educating people about the risks and benefits of vaccination. Most disease management programs have extensive experience in distributing educational materials and programs to health care workers and patients as well as in tracking response to interventions. Can this experience lend a hand in the event of widespread vaccination?

Smallpox and live-virus vaccination in transplant recipients.

PubMed

Fishman, Jay A

2003-07-01

Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately 30% in past outbreaks. Programs for smallpox immunization for healthcare workers have been proposed. Atypical forms of smallpox presenting with flat or hemorrhagic skin lesions are most common in individuals with immune deficits with historic mortality approaching 100%. Smallpox vaccination, even after exposure, is highly effective. Smallpox vaccine contains a highly immunogenic live virus, vaccinia. Few data exist for the impact of variola or safety of vaccinia in immunocompromised hosts. Both disseminated infection by vaccinia and person-to-person spread after vaccination are uncommon. When it occurs, secondary vaccinia has usually affected individuals with pre-existing skin conditions (atopic dermatitis or eczema) or with other underlying immune deficits. Historically, disseminated vaccinia infection was uncommon but often fatal even in the absence of the most severe form of disease, "progressive vaccinia". Some responded to vaccinia immune globulin. Smallpox exposure would be likely to cause significant mortality among immunocompromised hosts. In the absence of documented smallpox exposures, immunocompromised hosts should not be vaccinated against smallpox. Planning for bioterrorist events must include consideration of uniquely susceptible hosts.

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... documentation submitted under subpart F, the following: (1) Documentation showing that the deceased smallpox...

Control, containment and health education in the smallpox-vaccination campaigns in Mexico in the 1940s.

PubMed

Agostoni, Claudia

2015-01-01

This article examines some of the changes that the Mexican vaccination programs underwent starting in 1943, the year when the National Smallpox Campaign (Campaña Nacional contra la Viruela) was established. It analyzes why a uniform and coordinated vaccination method was adopted to counter the outbreaks of this endemic disease, especially in central Mexico; the actions of its numerous and heterogeneous staff; and the reasons why smallpox vaccination was considered critical to establish a culture of prevention. In summary, the article examines why selective vaccination was chosen and the expansion of the health-education programs, topics that have been seldom addressed in historical research.

Rethinking smallpox.

PubMed

Weiss, Martin M; Weiss, Peter D; Mathisen, Glenn; Guze, Phyllis

2004-12-01

The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

42 CFR 102.62 - Documentation an eligible requester seeking a death benefit must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To... smallpox vaccine recipient or vaccinia contact. If such a benefit(s) was provided, the requester must... vaccine recipient or vaccinia contact is survived by one or more dependents younger than the age of 18...

A brief history of smallpox eradication in Iran.

PubMed

Azizi, Mohammad Hossein

2010-01-01

Smallpox, which currently is only of historical interest, was once one of the most terrible illnesses with high mortality and morbidity. In the late 18th century, the English physician and naturalist, Edward Jenner (1749 - 1823), discovered an efficient preventive technique against smallpox which he termed "vaccination". Afterwards, the practice of vaccination gradually became widespread when finally in 1979, the World Health Organization formally declared the global eradication of this fatal disease.Presented here is a brief account of smallpox eradication in Iran which started on a limited scale in the 19th century by the order of Abbas Mirza (1789 - 1833), the Crown Prince of Fath Ali Shah Qajar (reign from 1797 - 1834), and reinforced in 1848 by Mirza Taghi Khan Amir Kabir (1807 - 1852) the Prime Minster of Naser ad-Din Shah, and became more popular after the establishment of the Pasteur Institute in Tehran in 1921, where considerable doses of smallpox vaccine were produced. In addition, in subsequent years, a law that mandated public smallpox vaccination was passed by the Iranian parliament (Majles) in 1953 and eventually, the mass vaccination program led to the complete eradication of smallpox in Iran in 1978.

Smallpox eradication in West and Central Africa.

PubMed

Foege, W H; Millar, J D; Henderson, D A

1975-01-01

The history of smallpox eradication in the 20 countries of West and Central Africa from Mauritania to Zaire is recounted, including background, evolution of strategy, assessment, maintenance, costs, and significance of the campaign. Smallpox was endemic in these countries, peaking each year at the end of the spring dry season, usually occurring in isolated villages only periodically. The average case fatality was 14.5%, but twice as high in infants and older adults. Clinical exams showed that those with actual vaccination scars rarely got smallpox. The campaign was made feasible because of lyophilized heat-stable vaccine and bifurcated needles or jet injectors. The initial strategy called for mass vaccination and assessment of achieved vaccination. Between 1967 and 1969 100 million persons were vaccinated at collecting points; by 1972, 28 million more children had been protected. In 1966 an outbreak of 34 cases in Nigeria was blocked within 3 weeks of initiation of surveillance and containment. This effort also demonstrated that actual smallpox transmission was slow and relatively ineffective, and further that vaccination of contacts even after exposure was effective. The strategy was replaced by surveillance-containment begun in the seasonal low. The results were that smallpox disappeared within 5 months in an area of 12 million, and within 1 year in 19 of the 20 countries. Maintenance vaccination to prevent importation of the virus is continuing. The cost of the program was $15 million to the U.S. sponsors, or 1/10 the yearly price of smallpox control in the U.S.

Smallpox and smallpox vaccine: ocular and systemic risks and ethical uncertainties.

PubMed

Chous, A Paul; Hom, Gregory G

2003-09-01

The threat of bioterrorism and use of biological weapons has drawn renewed attention to smallpox, and smallpox vaccinations have been resumed in the United States. Both smallpox and smallpox vaccine carry risk of potentially debilitating or fatal adverse effects. The optometrist must be familiar with the signs and symptoms of smallpox disease and complications of smallpox vaccine for proper management and preservation of vision. The literature on the ocular and systemic effects of smallpox and smallpox vaccination is reviewed to provide the practicing optometrist with an overview of the issues involved in case management. Recent guidelines have placed additional ocular-related contraindications to receiving the smallpox vaccine. Risk factors for complications arising from smallpox vaccination are discussed. A discussion of the ethical implications is also presented. Knowledge of the signs and symptoms of smallpox infection, and of adverse effects caused by smallpox vaccination, can provide the necessary background to help eye care providers make appropriate diagnoses and referrals. Understanding ethical and legal/Constitutional questions surrounding the risk of outbreak and various vaccination containment strategies will help optometrists make informed decisions as health care professionals, patient advocates, and concerned citizens, as well as weigh the risks and benefits of vaccination, if it is offered to them.

Smallpox vaccines for biodefense: need and feasibility.

PubMed

Artenstein, Andrew W; Grabenstein, John D

2008-10-01

Smallpox, eradicated as a cause of natural disease through an intensive global effort in the later part of the 20th Century, has resurfaced as a possible agent of bioterrorism. For this reason, there is renewed interest in smallpox vaccines. Live vaccinia virus, an orthopoxvirus related to smallpox, has a long and successful clinical track record as an effective smallpox vaccine; however, its use is associated with uncommon yet serious adverse events. This has led to a surge of recent research into newer-generation smallpox vaccines with improved safety profiles and retained efficacy. This article will review the history of smallpox vaccines, assess the status of newer-generation vaccines and examine the overall risk-versus-benefit profile of smallpox vaccination.

Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.

PubMed

Duraffour, Sophie; Andrei, Graciela; Snoeck, Robert

2010-03-01

Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.

Smallpox: vaccine reactions and contraindications.

PubMed

Tom, Wynnis L; Kenner, Julie R; Friedlander, Sheila F

2004-07-01

Concern regarding the use of smallpox for bioterrorism has led to the reintroduction of smallpox vaccination. The historic background leading to protective methods against smallpox disease, the adverse reactions and contraindications associated with vaccination, and the ongoing development of potentially safer smallpox vaccines are reviewed here.

The eradication of smallpox: organizational learning and innovation in international health administration.

PubMed

Hopkins, J W

1988-04-01

The WHO smallpox eradication campaign represents perhaps the best example of a successful international health administration. In the 1st year of the campaign (1967), the guiding strategy was to vaccinate people en masse over a 2-3 year period in countries where smallpox was epidemic thereby conquering the disease. In Western Nigeria where 90% of the population had been vaccinated, a smallpox outbreak occurred in a religious sect resisting vaccinations and a delay in delivery of supplies forced a change in strategy. Campaign staff learned to rapidly isolate infected persons and swiftly vaccinate the uninfected in an outbreak area in order to break the transmission of smallpox, even where 1/2 the population had been vaccinated. Technological advancements also contributed to the campaign's success. For example, the jet injector vaccinated 1000 people/hour with efficient, reliable, mass produced potent, stable freeze dried vaccines (often produced in target countries) or the less costly and virtually maintenance free bifurcated needle was used. The most significant contribution to the success of the campaign, however, was the flexible mode of management adopted by the campaign staff at WHO which provided an appropriate environment for organizational learning and innovation. Although management was open and flexible, the campaign did depend on careful planning and setting of goals, continual assessment, and rapid response to field requests for assistance or advice. Trends in the incidence of smallpox was chosen as the indicator of success as opposed to the number of vaccinations. The campaign demonstrated the need for cultural adaptations as it operated in each country and region. This evaluation of the success of the smallpox campaign presents conclusions that serve as guidelines to the organization and administration of international programs designed to solve other health problems.

A Case Series of Smallpox Vaccination-Associated Myopericarditis: Effects on Safety and Readiness of the Active Duty Soldier.

PubMed

Sarkisian, Simon A; Hand, Gregory; Rivera, Vanessa M; Smith, Meghan; Miller, Joel A

2018-06-27

Myopericarditis following smallpox vaccination is a documented side effect with increasing incidence since reestablishing mandatory vaccination for deploying military personnel. After the ACAM2000 smallpox vaccine replaced the Dryvax smallpox vaccine, the rate of myopericarditis increased 50-fold.We describe six case reports of active duty soldiers who presented to the emergency department complaining of chest pain shortly after receiving routine pre-deployment vaccinations to include smallpox. All were hospitalized and became non-deployable after developing smallpox vaccination-associated myopericarditis.Some cases of smallpox vaccination-associated myopericarditis are diagnosed in soldiers in austere environments, which have led to the soldier being removed from the mission for months at a time. This can be avoided by having all soldiers who receive the smallpox vaccine screened for clinical evidence of myopericarditis at 30 days after receiving the vaccine. Contributing to the increasing rate of myopericarditis as well as the negative impact on soldier medical readiness, the continued use of the current ACAM2000 smallpox vaccine should be monitored.

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens.

PubMed

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-02-05

The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.

Reflections on New York City's 1947 Smallpox Vaccination Program and Its 1976 Swine Influenza Immunization Program.

PubMed

Imperato, Pascal James

2015-06-01

In 1947, a smallpox outbreak occurred in New York City with a total of twelve cases and two deaths. In order to contain this outbreak, the New York City Department of Health launched a mass immunization campaign that over a period of some 60 days vaccinated 6.35 million people. This article examines in detail the epidemiology of this outbreak and the measures employed to contain it. In 1976, a swine influenza strain was isolated among a few recruits at a US Army training camp at Fort Dix, New Jersey. It was concluded at the time that this virus possibly represented a re-appearance of the 1918 influenza pandemic influenza strain. As a result, a mass national immunization program was launched by the federal government. From its inception, the program encountered a myriad of challenges ranging from doubts that it was even necessary to the development of Guillain-Barré paralysis among some vaccine recipients. This paper examines the planning for and implementation of the swine flu immunization program in New York City. It also compares it to the smallpox vaccination program of 1947. Despite equivalent financial and personnel resources, leadership and organizational skills, the 1976 program only immunized approximately a tenth of the number of New York City residents vaccinated in 1947. The reasons for these marked differences in outcomes are discussed in detail.

Smallpox vaccination and all-cause infectious disease hospitalization: a Danish register-based cohort study.

PubMed

Sørup, Signe; Villumsen, Marie; Ravn, Henrik; Benn, Christine Stabell; Sørensen, Thorkild I A; Aaby, Peter; Jess, Tine; Roth, Adam

2011-08-01

There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections. From the Copenhagen School Health Records Register, a cohort of 4048 individuals was sampled, of whom 3559 had information about receiving or not receiving smallpox vaccination. Infectious disease hospitalizations were identified in the Danish National Patient Register. During 87,228 person-years of follow-up, 1440 infectious disease hospitalizations occurred. Smallpox-vaccinated individuals had a reduced risk of all-cause infectious disease hospitalization compared with smallpox-unvaccinated individuals [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.72-0.98]. The reduced risk of hospitalizations was seen for most subgroups of infectious diseases. The effect may have been most pronounced after early smallpox vaccination (vaccination age <3.5 years: HR 0.81; 95% CI 0.69-0.95; vaccination age ≥ 3.5 years: HR 0.91 95% CI 0.76-1.10). Among the smallpox-vaccinated, the risk of infectious disease hospitalization increased 6% with each 1-year increase in vaccination age (HR 1.06; 95% CI 1.02-1.10). Smallpox vaccination is associated with a reduced risk of infectious disease hospitalization in a high-income setting.

Immunogenicity and Protection Efficacy of Subunit-based Smallpox Vaccines Using Variola Major Antigens

PubMed Central

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-01-01

The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on the VARV antigen sequences to induce immunity against poxvirus infection. PMID:17950773

Vaccine Basics (Smallpox)

MedlinePlus

... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases Vaccine Basics Recommend on Facebook ... Smallpox Website NIH Smallpox Research CDC Poxvirus and Rabies Branch Poxvirus Diseases File Formats Help: How do ...

Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

PubMed

Sato, Hajime

2011-09-01

Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

[Development of current smallpox vaccines].

PubMed

Maksiutov, R A; Gavrilova, E V; Shchelkunov, S N

2011-01-01

The review gives data on the history of smallpox vaccination and shows the high topicality of designing the current safe vaccines against orthopoxviruses. Four generations of live smallpox, protein subunit, and DNA vaccines are considered. Analysis of the data published leads to the conclusion that it is promising to use the up-to-date generations of safe smallpox subunit or DNA vaccines for mass primary immunization with possible further revaccination with classical live vaccine.

An open-label, single arm, phase III clinical study to evaluate the efficacy and safety of CJ smallpox vaccine in previously vaccinated healthy adults.

PubMed

Kim, Nak-Hyun; Kang, Yu Min; Kim, Gayeon; Choe, Pyoeng Gyun; Song, Jin Su; Lee, Kwang-Hee; Seong, Baik-Lin; Park, Wan Beom; Kim, Nam Joong; Oh, Myoung-don

2013-10-25

The increased possibility of bioterrorism has led to reinitiation of smallpox vaccination. In Korea, more than 30 years have passed since the last smallpox vaccinations, and even people who were previously vaccinated are not regarded as adequately protected against smallpox. We evaluated the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy adults previously vaccinated against smallpox. We conducted an open label, single arm, phase III clinical trial to evaluate the efficacy and safety of CJ-50300. Healthy volunteers, previously vaccinated against smallpox, born between 1950 and 1978 were enrolled. CJ-50300 was administered with a bifurcated needle over the deltoid muscle according to the recommended method. The rate of the cutaneous take reaction, humoral immunogenicity, and safety of the vaccine was assessed. Of 145 individuals enrolled for vaccination, 139 completed the study. The overall rates of cutaneous take reactions and humoral immunogenicity were 95.0% (132/139) and 88.5% (123/139), respectively. Although 95.9% (139/145) reported adverse events related to vaccination, no serious adverse reactions were observed. CJ-50300 can be used safely and effectively in healthy adults previously vaccinated against smallpox. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bioterrorism preparedness--Part II. Smallpox vaccination in a hospital setting.

PubMed

Jacobs, Lenworth M; Emanuelsen, Kathy; McKay, Charles; Burns, Karyl

2004-01-01

The threat of using smallpox as an agent for bioterrorism resulted in a directive for the creation of smallpox response teams. In Connecticut, The Commissioner of the Department of Public Health convened public health and hospital leadership to plan for the vaccination of these teams. The purpose of this paper is to provide a description of the vaccination program at Hartford Hospital, a Center of Excellence for Bioterrorism Preparedness, and to report the results of a survey of the vaccinees regarding the vaccination experience. Ninety persons were vaccinated. Six individuals experienced low-grade fever and 10 had axillary node swelling. One individual experienced significant fatigue. A total of six persons lost time from work. Four lost one day and two persons lost between four to five days of work. There was no autoinoculation, transfer inoculation, vaccinia or any other significant complication. Survey results indicate that most vaccinees felt positive about the experience.

Defending Against Smallpox: a Focus on Vaccines

PubMed Central

Voigt, Emily A.; Kennedy, Richard B.; Poland, Gregory A.

2016-01-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts. PMID:27049653

Defending against smallpox: a focus on vaccines.

PubMed

Voigt, Emily A; Kennedy, Richard B; Poland, Gregory A

2016-09-01

Smallpox has shaped human history, from the earliest human civilizations well into the 20th century. With high mortality rates, rapid transmission, and serious long-term effects on survivors, smallpox was a much-feared disease. The eradication of smallpox represents an unprecedented medical victory for the lasting benefit of human health and prosperity. Concerns remain, however, about the development and use of the smallpox virus as a biological weapon, which necessitates the need for continued vaccine development. Smallpox vaccine development is thus a much-reviewed topic of high interest. This review focuses on the current state of smallpox vaccines and their context in biodefense efforts.

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

42 CFR 102.20 - How to establish a covered injury.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.20 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... injuries. Minor injuries include expected and routine responses to the smallpox vaccine, other covered... smallpox vaccine recipient or vaccinia contact sustained an injury listed on the Smallpox (Vaccinia...

Smallpox: a review of clinical disease and vaccination.

PubMed

Lofquist, Jennifer M; Weimert, Nicole A; Hayney, Mary S

2003-04-15

The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination.

Logistics of community smallpox control through contact tracing and ring vaccination: a stochastic network model.

PubMed

Porco, Travis C; Holbrook, Karen A; Fernyak, Susan E; Portnoy, Diane L; Reiter, Randy; Aragón, Tomás J

2004-08-06

Previous smallpox ring vaccination models based on contact tracing over a network suggest that ring vaccination would be effective, but have not explicitly included response logistics and limited numbers of vaccinators. We developed a continuous-time stochastic simulation of smallpox transmission, including network structure, post-exposure vaccination, vaccination of contacts of contacts, limited response capacity, heterogeneity in symptoms and infectiousness, vaccination prior to the discontinuation of routine vaccination, more rapid diagnosis due to public awareness, surveillance of asymptomatic contacts, and isolation of cases. We found that even in cases of very rapidly spreading smallpox, ring vaccination (when coupled with surveillance) is sufficient in most cases to eliminate smallpox quickly, assuming that 95% of household contacts are traced, 80% of workplace or social contacts are traced, and no casual contacts are traced, and that in most cases the ability to trace 1-5 individuals per day per index case is sufficient. If smallpox is assumed to be transmitted very quickly to contacts, it may at times escape containment by ring vaccination, but could be controlled in these circumstances by mass vaccination. Small introductions of smallpox are likely to be easily contained by ring vaccination, provided contact tracing is feasible. Uncertainties in the nature of bioterrorist smallpox (infectiousness, vaccine efficacy) support continued planning for ring vaccination as well as mass vaccination. If initiated, ring vaccination should be conducted without delays in vaccination, should include contacts of contacts (whenever there is sufficient capacity) and should be accompanied by increased public awareness and surveillance.

Smallpox vaccine: problems and prospects.

PubMed

Poland, Gregory A; Neff, John M

2003-11-01

Smallpox justifiably is feared because of its morbidity and mortality. Wide-spread population-level susceptibility to smallpox exists, and the only effective tool against the virus is a live, attenuated vaccine that is highly reactogenic and controversial. A significant minority of the population has contraindications that prevent preexposure use of this vaccine. Newer, safer, and equally immunogenic vaccines must be developed and licensed. Several live, attenuated vaccines are in clinical trials. Although these vaccines may prove to be less reactogenic, they still may not be administered safely to a significant portion of the population because they contain live, attenuated viruses. Newer vaccines will be needed if routine preexposure vaccination is to be instituted universally. The idea of a subunit or peptide-based vaccine is appealing, because it obviates potential safety concerns. It may be possible to use a more-attenuated, live vaccine strain for a large segment of the population on a preexposure basis and accept the morbidity and mortality that would result from its use on a postexposure basis, if necessary. The need for widespread population-level protection against variola infection is apparent. The use of the new biology tools to predict or define who might experience serious reactions to the smallpox vaccine and why these reactions occur is an area ripe for additional research. The reason why an individual develops postvaccinal encephalitis remains unknown, and the development is unpredictable and untreatable. In the future, if the mechanism behind such adverse events is defined, it may be possible to screen persons who are likely to experience such events. Although the authors remain proponents for use of the vaccine in alignment with the CDC vaccination program and recommendations, the previous concerns indicate that new knowledge must be gained and shared. Further research on attenuated vaccines and nonliving or peptide vaccines with equal efficacy should remain the goal, as it is apparent that smallpox vaccine once again will become part of the vaccinologist's and public health official's armamentarium in the decades to come.

The Future of Smallpox Vaccination: is MVA the key?

PubMed Central

Slifka, Mark K

2005-01-01

Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity. PMID:15740619

Pre-event smallpox vaccination for healthcare workers revisited--the need for a carefully screened multidisciplinary cadre.

PubMed

Malone, John D

2007-03-01

As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia (smallpox) vaccinations were delivered with one fatality attributed to vaccination. Among 37901 United States civilian volunteer HCWs vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions - two were fatal. This older population had a higher rate of adverse events due to age-related coronary artery disease. T-cell mediated inflammatory processes induced by live vaccinia vaccination may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A carefully screened multidisciplinary cadre (physician, nurse, infection control practitioner, technician), pre-event vaccinated for smallpox, will supply the necessary leadership to alleviate fear and uncertainty while limiting spread and initial mortality of smallpox.

Anticipating smallpox and monkeypox outbreaks: complications of the smallpox vaccine.

PubMed

Abrahams, Brian C; Kaufman, David M

2004-09-01

The recent outbreak in the Midwest of monkeypox, as well as the continued fears of a terrorist-induced epidemic of smallpox, prompted the authors' review of the literature regarding past and current experiences with smallpox vaccination. The smallpox vaccine, which is highly effective in preventing the spread of both these orthopoxvirus infectious illnesses, might be administered to numerous health care workers and, in the event of a smallpox attack, millions of other citizens. However, vaccinees would be at risk for several vaccine-related neurologic complications. According to prior reports, neurologic complications have occurred in 2.5 per million US individuals, with the most common being postvaccinal encephalomyelitis (PVEM). In older children and adults, PVEM causes stupor and coma, seizures, paraparesis, and other neurologic and mental abnormalities, and, in 16% of cases, permanent neurologic sequelae. The overall mortality rate of neurologic complications is approximately 1.5 per million vaccinees. Risk factors for PVEM were age younger than 1 year and no previous smallpox vaccination, but not a prior episode of PVEM or other preexisting neurologic illnesses. Neither the current smallpox vaccination campaigns in Israel nor the one in the United States has had comparable complications, but the US campaign has been associated with myocarditis and myopericarditis. Although the potential neurologic complications of the smallpox vaccine must be weighed against the threat of monkeypox and smallpox, current experience with vaccination suggests it carries a very low risk of neurologic complications and does not lead to exacerbations of chronic neurologic illnesses.

Smallpox and pregnancy: from eradicated disease to bioterrorist threat.

PubMed

Suarez, Victor R; Hankins, Gary D V

2002-07-01

Health care personnel must be prepared for the threat of bioterrorism. Our objective is to educate primary care providers, obstetricians in particular, in the prevention, diagnosis, and treatment of smallpox. Smallpox poses a particularly serious threat because of its high case-fatality rate in unvaccinated populations (no one younger than 25 years has been vaccinated, and older persons have little remaining residual immunity). Routine nonemergency smallpox vaccination is restricted to laboratory staff working with smallpox-related viruses. Under these circumstances, contraindications to vaccination are pregnancy, immunodeficiency, exfoliative skin conditions (eczema), and allergy to vaccine components. In case of an intentional release of the smallpox virus, those directly exposed and their close contacts must be vaccinated and isolated. Under such emergency circumstances, pregnant women exposed to the variola virus should be vaccinated because of the lethality of the disease during pregnancy. Currently, there is a limited supply of vaccine available.

A population survey of smallpox knowledge, perceptions, and healthcare-seeking behavior surrounding the Iraq invasion--Connecticut 2002-03.

PubMed

Marshall, Katherine M; Begier, Elizabeth M; Griffith, Kevin S; Adams, Mary L; Hadler, James L

2005-01-01

Knowledge and perceptions about smallpox would probably influence public behavior following an intentional smallpox release. We assessed public knowledge, perceptions, and related healthcare-seeking behavior in Connecticut during the period of heightened interest in smallpox preparedness surrounding the Iraq invasion. Smallpox-related questions were added to Connecticut's Behavioral Risk Factor Surveillance System survey, an ongoing statewide adult population-based survey during December 2002-July 2003 and November-December 2003. Among 4,074 respondents, when asked about a hypothetical febrile illness, 72% would first contact their primary care provider (PCP) on weekdays. During nights and weekends, respondents would depend nearly equally on PCPs and emergency departments (37% versus 36%). Most knew smallpox is transmissible from person to person (72%) but not that the majority infected with smallpox survive (38%) or that smallpox is most contagious after the appearance of rash (11%). Knowledge regarding transmissibility and mortality improved during the study period (p < 0.001). Only 31% recognized that vaccinia vaccine is riskier than routine vaccines; 41% would choose vaccination if available. Concern about smallpox's potential use as a weapon was high but decreased after President Bush declared "mission accomplished" in Iraq in May 2003 (p < 0.001). Despite national coverage of smallpox by the media, most respondents lacked basic knowledge regarding the disease. Incorrect perceptions regarding vaccinia vaccine's risks could increase inappropriate vaccine demand among nonexposed people with vaccine contraindications during a mass vaccination campaign. Current perceptions should inform future smallpox preparedness planning. In addition, both PCPs and emergency medicine clinicians should be targeted for education regarding smallpox diagnosis.

Vaccines and bioterrorism: smallpox and anthrax.

PubMed

Kimmel, Sanford R; Mahoney, Martin C; Zimmerman, Richard K

2003-01-01

Because of the success of vaccination and the ring strategy in eradicating smallpox from the world, smallpox vaccine has not been recommended for the United States civilian populations for decades. Given the low but possible threat of bioterrorism, smallpox vaccination is now recommended for those teams investigating potential smallpox cases and for selected personnel of acute-care hospitals who would be needed to care for victims in the event of a terrorist attack. Treatment and post-exposure prophylaxis for anthrax are ciprofloxacin or doxycycline. Anthrax vaccine alone is not effective for post-exposure prevention of anthrax; vaccination is accompanied by 60 days of antibiotic therapy. In addition to military use, anthrax vaccine is recommended for pre-exposure use in those persons whose work involves repeated exposure to Bacillus anthracis spores.

Unraveling the structure of the variola topoisomerase IB-DNA complex: a possible new twist on smallpox therapy.

PubMed

Osheroff, Neil

2006-10-01

Smallpox is a serious and highly contagious disease that is caused by the variola virus. It is one of the most severe infectious human diseases known, with mortality rates as high as 30%. A successful worldwide vaccination program led to the eradication of smallpox in 1980. However, the high transmission rate of variola virus, coupled with the deadly nature of smallpox, makes this virus a potentially devastating weapon for bioterrorism. Currently, there is no specific treatment for smallpox. However, a recent article on the structure of a variola topoisomerase IB-DNA complex provides an intriguing starting point for the rational design of drugs with potential activity against smallpox.

Smallpox: what every otolaryngologist should know.

PubMed

Tennyson, Heath C; Mair, Eric A

2004-03-01

In light of recent terrorist events and the potential threat of smallpox as a biological agent, we present information concerning smallpox to better inform the otolaryngologist concerning this disease and its prevention. We performed a review of the smallpox and smallpox vaccination literature over the past 200 years using MEDLINE, PREMEDLINE, Centers for Disease Control and Prevention Internet site, World Health Organization Internet site, and references found in previous publications not found in MEDLINE or PREMEDLINE. Our search focused on the pathogenesis, clinical presentation, course, unique manifestations in the head and neck, diagnosis, and treatment of smallpox, as well as the method of smallpox vaccination, vaccination contraindications, and complications. Smallpox is a viral disease with a high mortality rate. Its clinical course, manifestations, and methods of prevention are carefully analyzed in light of otolaryngology practice. Smallpox manifestations in the head and neck often presented as acute airway obstruction and also as long-term sequelae such as ectropion, nasal vestibular stenosis, conductive hearing loss, and blindness. Most chronic sequelae involve the head and neck. Smallpox vaccination is effective but not without potential serious risks.

Smallpox vaccines: targets of protective immunity

PubMed Central

Moss, Bernard

2011-01-01

Summary The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second and third generation smallpox vaccines. PMID:21198662

Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence

PubMed Central

MacIntyre, C. Raina; Chen, Xin; Segelov, Eva; Chughtai, Abrar Ahmad; Kelleher, Anthony; Kunasekaran, Mohana; Lane, John Michael

2018-01-01

We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York’s and 17% of Sydney’s population are immunosuppressed. The highest smallpox infection rates were in persons 0–19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates. PMID:29553311

[Confronting bioterrorism: Epidemiologic, clinical, and preventive aspects of smallpox].

PubMed

Franco-Paredes, Carlos; del Río, Carlos; Nava-Frías, Margarita; Rangel-Frausto, Sigfrido; Téllez, Ildefonso; Santos-Preciado, José Ignacio

2003-01-01

The worldwide eradication of smallpox, a major achievement in public health, is currently threatened by the risk of bioterrorism. The debate on the destruction of the Variola virus in the two reference laboratories of the World Health Organization has dramatically switched to the preservation of the remaining virus after the September 2001 terrorist events in the U.S. along with the intentional release of Bacillus anthracis in the U.S. The risk of intentional release of Variola virus constitutes a minimal, yet possible risk. A smallpox epidemic could have a devastating impact due to its elevated morbidity and mortality that would inflict in non-immune human population, in addition to the ensuing panic and social unrest. Therefore, the development of national preparedness and response plans along with the availability of smallpox vaccine to be used in the post-exposure phase represent a fundamental part of the preventive efforts to cope with bioterrorism. Reestablishing a preventive vaccination program was recently recommended by the Advisory Committee on Immunization Practices (ACIP). However, the vaccine currently available has historically been associated with serious adverse reactions, even death. Thus, this recommendation has not been universally accepted. To counter an epidemic of smallpox, medical personnel in the frontline need to be prepared with updated smallpox information to identify, diagnose, isolate, and treat cases if a bioterrorist attack should occur. Herein we present an indepth review for health care personnel with relevant epidemiologic, clinical, and preventive information on smallpox.

Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate.

PubMed

Ferrier-Rembert, Audrey; Drillien, Robert; Meignier, Bernard; Garin, Daniel; Crance, Jean-Marc

2007-11-28

It is now difficult to manufacture the first-generation smallpox vaccine, as the process could not comply with current safety and manufacturing regulations. In this study, a candidate non-clonal second-generation smallpox vaccine developed by Sanofi-Pasteur from the Lister strain has been assessed using a cowpox virus challenge in mice. We have observed similar safety, immunogenicity and protection (from disease and death) after a short or long interval following vaccination, as well as similar virus clearance post-challenge, with the second-generation smallpox vaccine candidate as compared to the traditional vaccine used as a benchmark.

[Smallpox--historical or real threat].

PubMed

Zieliński, Andrzej; Stefanoff, Paweł

2004-01-01

Presently, there is no real possibility of natural re-emergence of smallpox virus, which was eradicated globally more then 25 years ago. During the last decade the possibility of use of smallpox virus as a biological weapon by a criminal organisation was emphasised. The re-emergence of smallpox virus would lead to unprecedented disaster. Theoretical models indicated that only extremely strict and enforced interventions could stop the spread of epidemic, but the assumptions of these models were unrealistic. Presently, there are limited stocks of the first generation smallpox vaccine left in the world. This vaccine, as well as the second-generation vaccine are associated with multiple adverse events, including fatalities and may not be accepted by society. Much safer vaccines are now being developed. Strategic plan of prophylactic vaccinations requires defining the groups to be immunised in the first place and whether immunisation should start before or after a first smallpox case would occur.

Smallpox vaccines: targets of protective immunity.

PubMed

Moss, Bernard

2011-01-01

The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. Published 2010. This article is a US Government work and is in the public domain in the USA.

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

42 CFR 102.46 - Amending a request package.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...) Requesters who are survivors. If a smallpox vaccine recipient or vaccinia contact submitted a Request Form...) Requests in which benefits are sought by the estate of a deceased smallpox vaccine recipient or vaccinia...

Antiviral immunity following smallpox virus infection: a case-control study.

PubMed

Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

2010-12-01

Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

PubMed Central

Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

2010-01-01

Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

42 CFR 102.32 - Benefits for lost employment income.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 102.32 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipients or vaccinia contacts may be able to receive benefits for loss of employment... may pay benefits for lost employment income to the estate of a deceased smallpox vaccine recipient or...

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.

PubMed

Stittelaar, Koert J; Neyts, Johan; Naesens, Lieve; van Amerongen, Geert; van Lavieren, Rob F; Holý, Antonin; De Clercq, Erik; Niesters, Hubert G M; Fries, Edwin; Maas, Chantal; Mulder, Paul G H; van der Zeijst, Ben A M; Osterhaus, Albert D M E

2006-02-09

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO-DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

42 CFR 102.41 - How to file a Request Package.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Compensation Program Office, Healthcare Systems Bureau, Health Resources and Services Administration, Parklawn... Smallpox Vaccine Injury Compensation Program Office, Healthcare Systems Bureau, Health Resources and...

[Smallpox--in the past or not?].

PubMed

Kuljić-Kapulica, Nada

2004-01-01

Smallpox is a potentially deadly illness caused by the variola virus, an orthopoxvirus. Severe illness followed by blister-like body rash is the sign of smallpox. Smallpox symptoms develop about 12 days after exposure. V. variole can spread very readily by aerosol, which may lead to explosive epidemics. For centuries, smallpox has been a worldwide cause of death, killing about 30% of the infected people. In 1972, the epidemic of smallpox in ex-Yugoslavia was the largest postwar smallpox epidemic in Europe. The total number of the affected was 175, out of whom 35 with fatal outcome, accounting for 20% of mortality. However, after a decade-long vaccination effort, the last natural case of smallpox occurred in 1977. The only way to prevent smallpox epidemic is by vaccination and patients' isolation. The possibility of future bioterrorism attacks, which may cause a new outbreak of smallpox and return variola, is very serious. World population is not immune, because of lack of vaccination. In 1980, the World Health Organization (WHO) declared the disease fully eradicated.

Pre-event Smallpox Vaccination for Healthcare Workers Revisited – the Need for a Carefully Screened Multidisciplinary Cadre

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malone, JD D.

2007-03-01

Abstract As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia vaccinations were delivered with 1 fatality attributed to vaccination. Among 37,901 U.S. civilian volunteer healthcare workers vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions – 2 were fatal.more » This older population had a higher rate of adverse events due to age related coronary artery disease. T-cell mediated inflammatory processes, induced by live vaccinia vaccination, may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A smallpox pre-vaccinated multidisciplinary cadre (physician, nurse, infection control practitioner, technician) will supply leadership to deal with fear and uncertainty while limiting spread and initial mortality of smallpox. Stochastic – from the Greek meaning “skillful in aiming” – is currently interpreted as arising from chance and involving probability. This issue’s article “Containing a large bioterrorist smallpox attack: a computer simulation approach” by Longini et al. is a discrete time, stochastic computer simulation model that offers additional planning guidance for a smallpox (variola virus) outbreak (1). Although interpretation of the model’s information may differ, Longini’s article concludes “Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths, but would require large numbers of prevaccinations” for the greatest effectiveness. In their simulation, the hospital has 686 workers (a relatively small facility compared to many tertiary care institutions) and 133 make close contact with smallpox cases prior to the initiation of isolation measures. Of 828 cases, 50% originated in the hospital and 13% of the contacts were untraceable. Preemptive smallpox (vaccinia virus) vaccination of 10% of the hospital workers, in addition to surveillance and containment, had a small effect on the average number of cases; however, preemptive vaccination of 50% of the hospital workers had a relatively large effect on case reduction. The larger number of preemptive vaccinations required less contact tracing and “ring” containment vaccinations. A delay of one day in fully implementing surveillance and containment resulted in a large epidemic.« less

Smallpox Vaccines for Biodefense

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna; Poland, Gregory A.

2009-01-01

Few diseases can match the enormous impact that smallpox has had on mankind. Its influence can be seen in the earliest recorded histories of ancient civilizations in Egypt and Mesopotamia. With fatality rates up to 30%, smallpox left its survivors with extensive scarring and other serious sequelae. It is estimated that smallpox killed 500 million people in the 19th and 20th centuries. Given the ongoing concerns regarding the use of variola as a biological weapon, this review will focus on the licensed vaccines as well as current research into next-generation vaccines to protect against smallpox and other poxviruses. PMID:19837292

The Spanish royal philanthropic expedition to bring smallpox vaccination to the New World and Asia in the 19th century.

PubMed

Franco-Paredes, Carlos; Lammoglia, Lorena; Santos-Preciado, José Ignacio

2005-11-01

The New World was ravaged by smallpox for several centuries after the Spanish conquest. Jenner's discovery of the smallpox vaccine made possible the prevention and control of smallpox epidemics. In response to a large outbreak of smallpox in the Spanish colonies, King Charles IV appointed Francisco Xavier de Balmis to lead an expedition that would introduce Jenner's vaccine to these colonies. During the journey, the vaccine was kept viable by passing it from arm to arm in orphaned children, who were brought along expressly for that purpose and remained under the care of the orphanage's director. This expedition was the first large scale mass vaccination of its kind. The historic legacy of this pioneering event in international health should be revisited in the current era of persistent inequalities in global health.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

PubMed

Slike, Bonnie M; Creegan, Matthew; Marovich, Mary; Ngauy, Viseth

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations

PubMed Central

Slike, Bonnie M.; Creegan, Matthew

2017-01-01

Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5–10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10–20 years post vaccination. This contrasted with a comparator group of adults, ages 35–49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112–3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program. PMID:28046039

Impaired innate, humoral, and cellular immunity despite a take in smallpox vaccine recipients.

PubMed

Kennedy, Richard B; Poland, Gregory A; Ovsyannikova, Inna G; Oberg, Ann L; Asmann, Yan W; Grill, Diane E; Vierkant, Robert A; Jacobson, Robert M

2016-06-14

Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or "take" at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impaired Innate, Humoral, and Cellular Immunity Despite a Take in Smallpox Vaccine Recipients

PubMed Central

Kennedy, Richard B.; Poland, Gregory A.; Ovsyannikova, Inna G.; Oberg, Ann L.; Asmann, Yan W.; Grill, Diane E.; Vierkant, Robert A.; Jacobson, Robert M.

2017-01-01

Smallpox vaccine is highly effective, inducing protective immunity to smallpox and diseases caused by related orthopoxviruses. Smallpox vaccine efficacy was historically defined by the appearance of a lesion or “take” at the vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as “protected.” However, the development of a typical vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1,000) cohorts of recipients of either Dryvax® or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the smallpox vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated smallpox vaccines and/or effective antiviral therapy targets against poxvirus infections. PMID:27177944

Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

PubMed Central

Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

2009-01-01

Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

Urban inoculation and the decline of smallpox mortality in eighteenth‐century cities—a reply to Razzell†

PubMed Central

Boulton, Jeremy; Schwarz, Leonard

2015-01-01

Smallpox was probably the single most lethal disease in eighteenth‐century Britain but was reduced to a minor cause of death by the mid‐nineteenth century due to vaccination programmes post‐1798. While the success of vaccination is unquestionable, it remains disputed to what extent the prophylactic precursor of vaccination, inoculation, reduced smallpox mortality in the eighteenth century. Smallpox was most lethal in urban populations, but most researchers have judged inoculation to have been unpopular in large towns. Recently, however, Razzell argued that inoculation significantly reduced smallpox mortality of adults and older children in London in the last third of the eighteenth century. This article uses demographic evidence from London and Manchester to confirm previous findings of a sudden fall in adult smallpox mortality and a rise in the importance of smallpox in early childhood c. 1770. The nature of these changes is consistent with an increase in smallpox transmission in London and Manchester after 1770 and indicates that smallpox inoculation was insufficient to reduce smallpox mortality in large towns. It remains unclear whether inoculation could have operated to enhance smallpox transmission or whether changes in the properties of the smallpox virus drove the intensification of smallpox mortality among young children post‐1770. PMID:26900169

Urban inoculation and the decline of smallpox mortality in eighteenth-century cities-a reply to Razzell.

PubMed

Davenport, Romola J; Boulton, Jeremy; Schwarz, Leonard

2016-02-01

Smallpox was probably the single most lethal disease in eighteenth-century Britain but was reduced to a minor cause of death by the mid-nineteenth century due to vaccination programmes post-1798. While the success of vaccination is unquestionable, it remains disputed to what extent the prophylactic precursor of vaccination, inoculation, reduced smallpox mortality in the eighteenth century. Smallpox was most lethal in urban populations, but most researchers have judged inoculation to have been unpopular in large towns. Recently, however, Razzell argued that inoculation significantly reduced smallpox mortality of adults and older children in London in the last third of the eighteenth century. This article uses demographic evidence from London and Manchester to confirm previous findings of a sudden fall in adult smallpox mortality and a rise in the importance of smallpox in early childhood c . 1770. The nature of these changes is consistent with an increase in smallpox transmission in London and Manchester after 1770 and indicates that smallpox inoculation was insufficient to reduce smallpox mortality in large towns. It remains unclear whether inoculation could have operated to enhance smallpox transmission or whether changes in the properties of the smallpox virus drove the intensification of smallpox mortality among young children post-1770.

Revisiting Jenner's mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines.

PubMed

Damaso, Clarissa R

2018-02-01

In 1796, Edward Jenner developed the smallpox vaccine consisting of pustular material obtained from lesions on cows affected by so-called cow-pox. The disease, caused by cowpox virus, confers crossprotection against smallpox. However, historical evidence suggests that Jenner might have used vaccinia virus or even horsepox virus instead of cowpox virus. Mysteries surrounding the origin and nature of the smallpox vaccine persisted during the 19th century, a period of intense exchange of vaccine strains, including the Beaugency lymph. This lymph was obtained from spontaneous cases of cow-pox in France in 1866 and then distributed worldwide. A detailed Historical Review of the distribution of the Beaugency lymph supports recent genetic analyses of extant vaccine strains, suggesting the lymph was probably a vaccinia strain or a horsepox-like virus. This Review is a historical investigation that revisits the mysteries of the smallpox vaccine and reveals an intricate evolutionary relationship of extant vaccinia strains. Copyright © 2018 Elsevier Ltd. All rights reserved.

The immunology of smallpox vaccines

PubMed Central

Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

2010-01-01

In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

Smallpox and biological warfare: the case for abandoning vaccination of military personnel.

PubMed Central

Capps, L; Vermund, S H; Johnsen, C

1986-01-01

Smallpox was officially declared eradicated from the world in 1980. Earlier, in 1972, over 50 nations signed the Biological Weapons Convention renouncing this entire category of weapons. Despite this international agreement, both the United States and the Soviet Union continue to vaccinate their military troops against smallpox, thus implying that each fears the other might still use it in biological warfare. Vaccination is not a harmless procedure, and vaccinia infections continue to be reported in troops and their contacts. Negotiating an end to the vaccination of troops would be a final step in ending the fear of smallpox. PMID:2944401

[Smallpox, bioterrorism agent].

PubMed

Bossi, Philippe; Bricaire, François

2002-11-30

A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. Two viral strains of the smallpox virus, which belong to the Poxviridae and orthopoxvirus-type families, are known. They are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". Five clinical forms of varying prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe form of the disease), mild smallpox (predominantly observed in vaccinated patients), flat-type smallpox (defined by coalescent and slowly progressive lesions) and so-called "sine eruptione" smallpox. This form is not as severe as variola major and the mortality rate is lesser. Smallpox must be systematically evoked on clinical elements and confirmed by electronic microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains can be characterised by PCR (Polymerase Chain Reaction). It is symptomatic. Early vaccination, within 4 days following exposure to the virus, permits the reduction in mortality by 50%. The only efficient prevention is vaccination prior to any exposure to the virus. In the case of a bioterrorist attack, the United States and most of the EC countries propose to vaccinate only the health professionnals most exposed to the virus and those having contacted identified cases.

Smallpox

MedlinePlus

... is unknown how long past vaccinations stay effective. People who received the vaccine many years ago may no longer be fully ... you have been exposed through bioterrorism. Prevention Many people were vaccinated against smallpox in the past. The vaccine is no longer given to the general public. ...

[The late media emergency of smallpox vaccine, news coverage of Spanish press (1999-2004)].

PubMed

Martínez-Martínez, Pedro Javier; Tuells, José; Colmenar-Jarillo, Gema

2015-06-01

Discussions on the need for smallpox virus preservation in 1999 focused attention on an eradicated disease 20 years ago. Smallpox was replaced as a potential candidate to be used as a bioterrorist weapon because of the international alarm scenario produced after the 11/9 events in USA. The reactivation of a vaccine which remained forgotten was the direct consequence. The initial target groups were the security forces of America. Spain was also among the countries that were interested in acquiring the smallpox vaccine. The aim of this study is to analyze the considerable media coverage of smallpox obtained in our country. Systematic review of published news in the four largest national daily newspapers (ABC, El Mundo, El País and La Vanguardia) for the period 1999-2004 of the Dow Jones Factiva document database. "Smallpox" were used as a key word. From the obtained data, a qualitative and quantitative analysis was done. 416 reviews were analyzed; the newspaper El Mundo was the most interested in these news (158 citations, 37.98%). Most of the news were published in 2003 (152, 36.5%) The year with more news about smallpox (2003) coincides with the purchase of vaccines in Spain. The type of messages in the news was highly changeable over this six-year period. Those related to "politics and diplomacy", "epidemiological risk", "bioterrorism" and "vaccine" were predominant. The alarm raised around the smallpox vaccination was a media phenomenon due to political strategy issues rather than a real public health problem.

[Strategies, actors, promises and fears in the smallpox vaccinations campaigns in Mexico: from the Porfiriato to the Post-revolution (1880-1940)].

PubMed

Agostoni, Claudia

2011-02-01

The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.

Smallpox.

PubMed

Nafziger, Sarah D

2005-10-01

Smallpox is a highly infectious disease, which, in 1980, was declared eradicated by the World Health Organization as a result of successful vaccination campaigns. Because of its highly infectious nature and historical 30% mortality rate, the disease has possibly been developed as a biological weapon. Variola, the virus that causes smallpox, is readily transmissible from person to person during the incubation period, before infected individuals show signs of illness. When a victim develops the characteristic rash and viral syndrome associated with smallpox infection, the disease requires complex isolation and possibly quarantine. Diagnosis can be confirmed in a high-containment laboratory. The only effective treatment for smallpox is rapid administration of smallpox vaccine.

THE EFFECT OF GAMMA-RAYS OF Co$sup 60$ ON SMALLPOX VACCINE CONTAMINATING MICROORGANISMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalenina, E.F.; Abidov, A.Z.

1963-02-01

Liquid smallpox vaccine inactivated by gamma irradiation proved to be fully adequate for studying the effects of gamma irradiation on the viability of microorganism artificially added to it. The complete inactivation of Staphylococcus albus and Bacillus subtilis, which most frequently contaminate smallpox vaccine, occurs by gamma irradiation from Co/sup 60/ ranging from 900,000 to 1.5-million r doses at 47 impulses/second magnitude. (OTS)

Smallpox.

PubMed

Goozé, Lisa L; Hughes, Elizabeth C W

2003-09-01

Until the 1970s, smallpox was feared worldwide for the significant morbidity and mortality it caused. Although naturally occurring disease has been eliminated, the virus itself has not been destroyed, and it is assumed that some of the variola stored in the former Soviet Union has been removed. The majority of the world's population is susceptible to smallpox because vaccination ended in 1972 in the United States and in the rest of the world in 1982. A major epidemic could result if there was an intentional release of smallpox. Variola is both durable and highly infective, 2 features that make it an attractive bioweapon. Because of this threat, physicians should be familiar with the clinical features of smallpox and the appropriate isolation and medical response procedures. Although there is a vaccine that can provide pre- and postexposure protection, the vaccination itself is not without risks. There is no effective therapy for smallpox and studies of new treatments are underway.

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study.

PubMed

Villumsen, Marie; Sørup, Signe; Jess, Tine; Ravn, Henrik; Relander, Thomas; Baker, Jennifer L; Benn, Christine Stabell; Sørensen, Thorkild I A; Aaby, Peter; Roth, Adam

2009-11-16

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N=2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.

Why, which, how, who, when? A personal view of smallpox vaccination for the 2000s.

PubMed

Mortimer, P P

2004-06-01

The uncertainty about the extent of proliferation of smallpox virus holdings since the early 1990s, and particularly whether terrorist groups or so-called rogue states might now hold the virus, confronts potential target countries with a continuing dilemma. An increasingly large majority of their populations have never been vaccinated, and those who have been vaccinated may have become susceptible to smallpox again. Yet recent attempts by the United States and other governments to persuade large numbers of key personnel and others to accept vaccination have at least partially failed and a different long-term strategy is needed. This strategy should be based on surveillance of rash illnesses, improved public education, more refined contingency planning and a new approach to smallpox vaccination. The last should if possible be based on cell-grown, less reactogenic vaccines, even though it may be some years before these can become available. Meanwhile this article examines other expedients including the use of existing lymph vaccines.

Standardized emergency management system and response to a smallpox emergency.

PubMed

Kim-Farley, Robert J; Celentano, John T; Gunter, Carol; Jones, Jessica W; Stone, Rogelio A; Aller, Raymond D; Mascola, Laurene; Grigsby, Sharon F; Fielding, Jonathan E

2003-01-01

The smallpox virus is a high-priority, Category-A agent that poses a global, terrorism security risk because it: (1) easily can be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential for a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. In recognition of this risk, the Los Angeles County Department of Health Services (LAC-DHS) developed the Smallpox Preparedness, Response, and Recovery Plan for LAC to prepare for the possibility of an outbreak of smallpox. A unique feature of the LAC-DHS plan is its explicit use of the Standardized Emergency Management System (SEMS) framework for detailing the functions needed to respond to a smallpox emergency. The SEMS includes the Incident Command System (ICS) structure (management, operations, planning/intelligence, logistics, and finance/administration), the mutual-aid system, and the multi/interagency coordination required during a smallpox emergency. Management for incident command includes setting objectives and priorities, information (risk communications), safety, and liaison. Operations includes control and containment of a smallpox outbreak including ring vaccination, mass vaccination, adverse events monitoring and assessment, management of confirmed and suspected smallpox cases, contact tracing, active surveillance teams and enhanced hospital-based surveillance, and decontamination. Planning/intelligence functions include developing the incident action plan, epidemiological investigation and analysis of smallpox cases, and epidemiological assessment of the vaccination coverage status of populations at risk. Logistics functions include receiving, handling, inventorying, and distributing smallpox vaccine and vaccination clinic supplies; personnel; transportation; communications; and health care of personnel. Finally, finance/administration functions include monitoring costs related to the smallpox emergency, procurement, and administrative aspects that are not handled by other functional divisions of incident command systems. The plan was developed and is under frequent review by the LAC-DHS Smallpox Planning Working Group, and is reviewed periodically by the LAC Bioterrorism Advisory Committee, and draws upon the Smallpox Response Plan and Guidelines of the Centers for Disease Control and Prevention (CDC) and recommendations of the Advisory Committee on Immunization Practices (ACIP). The Smallpox Preparedness, Response, and Recovery Plan, with its SEMS framework and ICS structure, now is serving as a model for the development of LAC-DHS plans for responses to other terrorist or natural-outbreak responses.

Immunomodulator-based enhancement of anti smallpox immune responses.

PubMed

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.

Immunomodulator-Based Enhancement of Anti Smallpox Immune Responses

PubMed Central

Martínez, Osmarie; Miranda, Eric; Ramírez, Maite; Santos, Saritza; Rivera, Carlos; Vázquez, Luis; Sánchez, Tomás; Tremblay, Raymond L.; Ríos-Olivares, Eddy; Otero, Miguel

2015-01-01

Background The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein. Methods We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation. Results The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections. Conclusion These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform. PMID:25875833

The decline of adult smallpox in eighteenth-century London.

PubMed

Davenport, Romola; Schwarz, Leonard; Boulton, Jeremy

2011-01-01

Smallpox was probably the single most lethal disease in eighteenth-century Britain, but was a minor cause of death by the mid-nineteenth century. Although vaccination was crucial to the decline of smallpox, especially in urban areas, from the beginning of the nineteenth century, it remains disputed the extent to which smallpox mortality declined before vaccination. Analysis of age-specific changes in smallpox burials within the large west London parish of St Martin-in-the-Fields revealed a precipitous reduction in adult smallpox risk from the 1770s, and this pattern was duplicated in the east London parish of St Dunstan's. Most adult smallpox victims were rural migrants, and such a drop in their susceptibility is consistent with a sudden increase in exposure to smallpox in rural areas. We investigated whether this was due to the spread of inoculation, or an increase in smallpox transmission, using changes in the age patterns of child smallpox burials. Smallpox mortality rose among infants, and smallpox burials became concentrated at the youngest ages, suggesting a sudden increase in infectiousness of the smallpox virus. Such a change intensified the process of smallpox endemicization in the English population, but also made cities substantially safer for young adult migrants.

Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence?

PubMed Central

Olson, Victoria A.; Shchelkunov, Sergei N.

2017-01-01

Smallpox was the first human disease to be eradicated, through a concerted vaccination campaign led by the World Health Organization. Since its eradication, routine vaccination against smallpox has ceased, leaving the world population susceptible to disease caused by orthopoxviruses. In recent decades, reports of human disease from zoonotic orthopoxviruses have increased. Furthermore, multiple reports of newly identified poxviruses capable of causing human disease have occurred. These facts raise concerns regarding both the opportunity for these zoonotic orthopoxviruses to evolve and become a more severe public health issue, as well as the risk of Variola virus (the causative agent of smallpox) to be utilized as a bioterrorist weapon. The eradication of smallpox occurred prior to the development of the majority of modern virological and molecular biological techniques. Therefore, there is a considerable amount that is not understood regarding how this solely human pathogen interacts with its host. This paper briefly recounts the history and current status of diagnostic tools, vaccines, and anti-viral therapeutics for treatment of smallpox disease. The authors discuss the importance of further research to prepare the global community should a smallpox-like virus emerge.

Remaining questions about clinical variola major.

PubMed

Lane, J Michael

2011-04-01

After the recent summary of World Health Organization-authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.

Freeze-dried live attenuated smallpox vaccine prepared in cell culture "LC16-KAKETSUKEN": Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice.

PubMed

Nishiyama, Yasumasa; Fujii, Tatsuya; Kanatani, Yasuhiro; Shinmura, Yasuhiko; Yokote, Hiroyuki; Hashizume, So

2015-11-09

In Japan, production of smallpox vaccine LC16m8 (named LC16-KAKETSUKEN) was restarted and was determined to be maintained as a national stockpile in March 2002. To conduct a post-marketing surveillance study of the vaccination of freeze-dried live attenuated smallpox vaccine prepared in cell culture LC16-KAKETSUKEN using attenuated vaccinia strain LC16m8. The study complied with Good Clinical Practice, focusing on a comparison between primary vaccinees and re-vaccinees. 268 personnel (261 males and 7 females) of the Japan Ground Self-Defense Force were inoculated with LC16-KAKETSUKEN and thereafter adverse events and efficacy were evaluated. Among 268 vaccinee participants, the following vaccinees showed adverse events, none serious: 53 of 196 primary vaccinees (without previous smallpox vaccination), 4 of 71 re-vaccinees (with previous smallpox vaccination) and 1 vaccinee with unknown previous vaccination history. A breakdown of adverse events observed in this study (total 268 vaccinees) showed the following minor or mild adverse events: 52 (19.4%) swelling of axillary lymph node, 4 (1.5%) fever, 2 (0.7%) fatigue, 1 (0.4%) of rash, 14 (5.2%) erythema at the inoculation site, 1 (0.4%) swelling at the inoculation site and 1 (0.4%) autoinoculation. The incidence of adverse events for primary vaccinees (53/196; 27.0%) was significantly higher than for re-vaccinees (4/71; 5.6%). However, the proportion of vaccine take was significantly higher for primary vaccinees (185/196; 94.4%) than for re-vaccinees (58/71; 81.7%). Although the proportion of vaccine take of re-vaccinees was significantly lower than for primary vaccinees due to preexisting immunity by previous vaccination, no significant difference was found in neutralizing antibody titers between primary vaccinees and re-vaccinees at 1, 4 and 7 months after LC16-KAKETSUKEN vaccination. The present post-marketing surveillance study compliant with Good Clinical Practice demonstrated the efficacy and safety of the smallpox vaccine LC16-KAKETSUKEN in an adult population. LC16-KAKETSUKEN is the sole currently available licensed smallpox vaccine for both adult and pediatric populations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effect of Smallpox and Bacillus Calmette-Guérin Vaccination on the Risk of Human Immunodeficiency Virus-1 Infection in Guinea-Bissau and Denmark

PubMed Central

Villumsen, Marie; Jensen, Mette Lundsby; Ravn, Henrik; da Silva, Zacarias J; Sørup, Signe; Baker, Jennifer Lyn; Rodrigues, Amabélia; Benn, Christine Stabell; Roth, Adam E; Aaby, Peter

2017-01-01

Abstract Background The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. Methods We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. Results Bacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36–1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43–1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46–0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10–0.75) as follows: women, aOR = 0.18 (95% CI, 0.05–0.64); men, aOR = 0.52 (95% CI, 0.12–2.33); sex-differential effect, P = .29. Conclusions The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine. PMID:28852677

Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

PubMed

Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

2015-08-26

The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses.

PubMed

Couch, Robert B; Winokur, Patricia; Edwards, Kathryn M; Black, Steven; Atmar, Robert L; Stapleton, Jack T; Kissner, Jennifer M; Shinefield, Henry; Denny, Thomas N; Bybel, Michael J; Newman, Frances K; Yan, Lihan

2007-03-15

When the decision was made to prepare for a deliberate release of smallpox, the United States had approximately 15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified approximately 85 million additional doses in storage. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Estimated doses of 10(6.6)-10(8.2) pfu of virus/mL induced major reactions (or "takes") in 93%-100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 10(6.6)-10(7.2) pfu/mL than for those given doses of 10(7.6)-10(8.2) pfu/mL. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine.

Therapeutic vaccination to treat chronic infectious diseases

PubMed Central

Boukhebza, Houda; Bellon, Nadine; Limacher, Jean Marc; Inchauspé, Geneviève

2012-01-01

A famous milestone in the vaccine field has been the first successful vaccination against smallpox, in 1798, by Edward Jenner. Using the vaccinia cowpox virus, Jenner was able to protect vaccinees from variola or smallpox. The Modified Virus Ankara (MVA) poxvirus strain has been one of the vaccines subsequently developed to prevent smallpox infection and was selected by the US government in their Biodefense strategy. Progress in molecular biology and immunology associated with MVA infection has led to the development of MVA as vaccine platform, both in the field of preventive and therapeutic vaccines. This later class of therapeutics has witnessed growing interest that has translated into an increasing number of vaccine candidates reaching the clinics. Among those, MVA-based therapeutic vaccines have addressed four major chronic infections including viral hepatitis, AIDS, human papillomavirus-linked pathologies and tuberculosis. Clinical trials encompass phase 1 and 2 and have started to show significant results and promises. PMID:22894957

The effects of post-exposure smallpox vaccination on clinical disease presentation: addressing the data gaps between historical epidemiology and modern surrogate model data.

PubMed

Keckler, M Shannon; Reynolds, Mary G; Damon, Inger K; Karem, Kevin L

2013-10-25

Decades after public health interventions - including pre- and post-exposure vaccination - were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effects of post-exposure smallpox vaccination on clinical disease presentation: Addressing the data gaps between historical epidemiology and modern surrogate model data

PubMed Central

Keckler, M. Shannon; Reynolds, Mary G.; Damon, Inger K.; Karem, Kevin L.

2015-01-01

Decades after public health interventions – including pre- and post-exposure vaccination – were used to eradicate smallpox, zoonotic orthopoxvirus outbreaks and the potential threat of a release of variola virus remain public health concerns. Routine prophylactic smallpox vaccination of the public ceased worldwide in 1980, and the adverse event rate associated with the currently licensed live vaccinia virus vaccine makes reinstatement of policies recommending routine pre-exposure vaccination unlikely in the absence of an orthopoxvirus outbreak. Consequently, licensing of safer vaccines and therapeutics that can be used post-orthopoxvirus exposure is necessary to protect the global population from these threats. Variola virus is a solely human pathogen that does not naturally infect any other known animal species. Therefore, the use of surrogate viruses in animal models of orthopoxvirus infection is important for the development of novel vaccines and therapeutics. Major complications involved with the use of surrogate models include both the absence of a model that accurately mimics all aspects of human smallpox disease and a lack of reproducibility across model species. These complications limit our ability to model post-exposure vaccination with newer vaccines for application to human orthopoxvirus outbreaks. This review seeks to (1) summarize conclusions about the efficacy of post-exposure smallpox vaccination from historic epidemiological reports and modern animal studies; (2) identify data gaps in these studies; and (3) summarize the clinical features of orthopoxvirus-associated infections in various animal models to identify those models that are most useful for post-exposure vaccination studies. The ultimate purpose of this review is to provide observations and comments regarding available model systems and data gaps for use in improving post-exposure medical countermeasures against orthopoxviruses. PMID:23994378

Modeling potential responses to smallpox as a bioterrorist weapon.

PubMed

Meltzer, M I; Damon, I; LeDuc, J W; Millar, J D

2001-01-01

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by > or = 33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

Smallpox virus destruction and the implications of a new vaccine.

PubMed

Henderson, D A

2011-06-01

The World Health Assembly is scheduled to decide in May 2011 whether the 2 known remaining stockpiles of smallpox virus are to be destroyed or retained. In preparation for this, a WHO-appointed committee undertook a comprehensive review of the status of smallpox virus research from 1999 to 2010. It concluded that, considering the nature of the studies already completed with respect to vaccine, drugs, and diagnostics, there was no reason to retain live smallpox virus except to satisfy restrictive regulatory requirements. The committee advised that researchers and regulators define alternative models for testing the vaccines and drugs. Apart from other considerations, the costs of new products are significant and important. These include prospective expenditures required for the development, manufacture, testing, and storage of new products. This commentary provides approximations of these costs and the incremental contribution that a newly developed vaccine might make in terms of public health security.

Comparison of smallpox outbreak control strategies using a spatial metapopulation model.

PubMed

Hall, I M; Egan, J R; Barrass, I; Gani, R; Leach, S

2007-10-01

To determine the potential benefits of regionally targeted mass vaccination as an adjunct to other smallpox control strategies we employed a spatial metapopulation patch model based on the administrative districts of Great Britain. We counted deaths due to smallpox and to vaccination to identify strategies that minimized total deaths. Results confirm that case isolation, and the tracing, vaccination and observation of case contacts can be optimal for control but only for optimistic assumptions concerning, for example, the basic reproduction number for smallpox (R0=3) and smaller numbers of index cases ( approximately 10). For a wider range of scenarios, including larger numbers of index cases and higher reproduction numbers, the addition of mass vaccination targeted only to infected districts provided an appreciable benefit (5-80% fewer deaths depending on where the outbreak started with a trigger value of 1-10 isolated symptomatic individuals within a district).

Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.

PubMed

Jones, Dorothy I; McGee, Charles E; Sample, Christopher J; Sempowski, Gregory D; Pickup, David J; Staats, Herman F

2016-07-01

Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine.

PubMed

Ferrier-Rembert, Audrey; Drillien, Robert; Tournier, Jean-Nicolas; Garin, Daniel; Crance, Jean-Marc

2008-03-25

This study assessed three non-replicating smallpox vaccine candidates (modified vaccinia Ankara (MVA), NYVAC and HR) for their immunogenicity and ability to protect mice against an intranasal cowpox virus challenge and compared them with the traditional replicating vaccine. A single immunisation with the non-replicating vaccines induced a complete protection from death at short-term, but was not fully protective when mice were challenged 150 days post-vaccination with protection correlated with the specific neutralizing antibodies and CD4(+) T-cells responses. Prime-boost vaccination enabled effective long-term protection from death for mice vaccinated with MVA, but protection from disease and CD4(+) T-cell level were lower than the ones induced by the traditional vaccine over the long-term period. Further investigations are necessary with MVA to determine the optimal conditions of immunisation to induce at long-term immunogenicity and protection observed with the 1st generation smallpox vaccine.

Smallpox Control in Canada

PubMed Central

Best, E. W. R.; Davies, J. W.

1965-01-01

During the period 1961 to 1963 there were 10 separate importations of smallpox cases by aircraft into England and Wales, Germany, Sweden, Poland and Canada. A feature of the resulting outbreaks was the number of cases and deaths of physicians and other health personnel. With the increasing volume of international air traffic there is a risk of importing incubating cases of smallpox into Canada, as occurred in 1962. Millions of Canadians have been protected against smallpox. Some complications of smallpox vaccination have occurred in Canada; such complications can be minimized by proper attention to contraindications to vaccination. The Food and Drug Directorate, Department of National Health and Welfare, has circularized all physicians in Canada to request their co-operation in reporting adverse reactions to drugs. This includes serious, unusual or unsuspected reactions to immunizing agents (vaccines, toxoids and antitoxins). The latter information will be shared with the Epidemiology Division, Department of National Health and Welfare, and the provincial epidemiologist and manufacturer concerned. The importance of maintaining the smallpox immunity of physicians, nurses and other hospital and health personnel in Canada is emphasized. PMID:14296005

Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.

PubMed

Thorne, Craig D; Hirshon, Jon Mark; Himes, Carrie D; McDiarmid, Melissa A

2003-11-01

In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families.

A brief history of vaccines & vaccination in India.

PubMed

Lahariya, Chandrakant

2014-04-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19 th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts.

A brief history of vaccines & vaccination in India

PubMed Central

Lahariya, Chandrakant

2014-01-01

The challenges faced in delivering lifesaving vaccines to the targeted beneficiaries need to be addressed from the existing knowledge and learning from the past. This review documents the history of vaccines and vaccination in India with an objective to derive lessons for policy direction to expand the benefits of vaccination in the country. A brief historical perspective on smallpox disease and preventive efforts since antiquity is followed by an overview of 19th century efforts to replace variolation by vaccination, setting up of a few vaccine institutes, cholera vaccine trial and the discovery of plague vaccine. The early twentieth century witnessed the challenges in expansion of smallpox vaccination, typhoid vaccine trial in Indian army personnel, and setting up of vaccine institutes in almost each of the then Indian States. In the post-independence period, the BCG vaccine laboratory and other national institutes were established; a number of private vaccine manufacturers came up, besides the continuation of smallpox eradication effort till the country became smallpox free in 1977. The Expanded Programme of Immunization (EPI) (1978) and then Universal Immunization Programme (UIP) (1985) were launched in India. The intervening events since UIP till India being declared non-endemic for poliomyelitis in 2012 have been described. Though the preventive efforts from diseases were practiced in India, the reluctance, opposition and a slow acceptance of vaccination have been the characteristic of vaccination history in the country. The operational challenges keep the coverage inequitable in the country. The lessons from the past events have been analysed and interpreted to guide immunization efforts. PMID:24927336

The new ACAM2000 vaccine and other therapies to control orthopoxvirus outbreaks and bioterror attacks.

PubMed

Handley, Lauren; Buller, Robert Mark; Frey, Sharon E; Bellone, Clifford; Parker, Scott

2009-07-01

Quarantine, case tracing and population vaccination facilitated the global eradication, in 1980, of variola virus, the causative agent of smallpox. The vaccines used during the eradication period, including Dryvax, the smallpox vaccine used in the USA, were live vaccinia and cowpoxvirus-based vaccines, which induced long-lasting and cross-protective immunity against variola and other related poxviruses. These vaccine viruses were produced by serial propagation in domesticated animals. The drawbacks to such serially propagated live viral vaccines include the level of postvaccination local and systemic reactions and contraindications to their use in immunocompromised individuals, individuals with certain skin and cardiac diseases, and pregnant women. In the latter stages of the population-based smallpox vaccination campaign, research began with ways to improve safety and modernizing the manufacture of vaccinia vaccines; however, with the eradication of variola this work stopped. Outbreaks of monkeypoxvirus in humans and the bioterrorist threat of monkeypox and variola virus renewed the need for improved vaccinia vaccines. ACAM2000 is one of the new generation of smallpox vaccines. It is produced in cell culture from a clonally purified master seed stock of vaccinia derived from the New York City Board of Health strain of vaccinia. The clonally purified master seed assures a more homogeneous vaccine without the inherent mutations associated with serial propagation and the cell culture limits adventitious and bacterial contamination in vaccine production. In preclinical and clinical trials, ACAM2000 demonstrated an immunogenicity and safety profile similar to that of Dryvax.

Analysis of variola and vaccinia virus neutralization assays for smallpox vaccines.

PubMed

Hughes, Christine M; Newman, Frances K; Davidson, Whitni B; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Yan, Lihan; Frey, Sharon E; Belshe, Robert B; Karem, Kevin L; Damon, Inger K

2012-07-01

Possible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector.

PubMed

Pavot, Vincent; Sebastian, Sarah; Turner, Alison V; Matthews, Jake; Gilbert, Sarah C

2017-01-01

The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant properties, and induces humoral and cellular immune responses. Many clinical trials of these new vaccines have been conducted, and the safety of MVA is now well documented. Immunogenicity is influenced by the dose and vaccination regimen, and information on the efficacy of MVA-vectored vaccines is now beginning to accumulate. In this chapter, we provide protocols for generation, isolation, amplification, and purification of recombinant MVA for preclinical and clinical evaluation.

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus

PubMed Central

Delaune, Déborah; Iseni, Frédéric; Ferrier-Rembert, Audrey; Peyrefitte, Christophe N.; Ferraris, Olivier

2017-01-01

Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses. PMID:29295488

Challenges and Achievements in Prevention and Treatment of Smallpox

PubMed Central

Melamed, Sharon; Israely, Tomer; Paran, Nir

2018-01-01

Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions. PMID:29382130

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

42 CFR 102.45 - Multiple survivors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Multiple survivors. 102.45 Section 102.45 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... smallpox vaccine recipient or vaccinia contact may file Request Forms separately or together. Multiple...

Smallpox vaccination: an early start of modern medicine in America.

PubMed

Liebowitz, Dan

2017-01-01

Smallpox was eradicated by the World Health Organization in 1980. Before its eradication thedisease had a mortality rate upwards of 50% and had a significant impact on society. During theAmerican Revolutionary war, smallpox outbreaks were impeding the American war effort until1777 when George Washington carried out a mass inoculation campaign in the ContinentalArmy that reduced the mortality from smallpox to less than 2%. Inoculation was an early formof vaccination that used live virus from active pustules to induce a milder, but still sometimesdeadly, case of disease. Washington has been credited with helping to ease the burden ofsmallpox on the Army which improved the odds of success against the British. When EdwardJenner's vaccine reached America it was more readily accepted by political and medical leadersdue the success of Washington's inoculation campaign. The Founding Fathers argued thatsmallpox vaccination was the greatest discovery in modern medicine and they were likely correctthat it helped to usher in the modern era of vaccinology.

Evaluation of smallpox vaccines using variola neutralization.

PubMed

Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

2009-08-01

The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial.

PubMed

Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2015-04-01

Background.  First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods.  An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results.  Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions.  Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

42 CFR 102.84 - The Secretary's right to recover benefits paid under this program from third-party payors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false The Secretary's right to recover benefits paid under this program from third-party payors. 102.84 Section 102.84 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of...

Smallpox

MedlinePlus

... of the variola virus that causes smallpox were saved in laboratories. Some people have expressed concern that terrorists could try to ... the virus make the illness less severe in people who do become infected if ... days Can Vaccines Stop a Smallpox Outbreak? After the September 11, ...

Self-reported Adverse Health Events Following Smallpox Vaccination in a Large Prospective Study of US Military Service Members

DTIC Science & Technology

2007-08-27

bullous erythema multiforme (Stevens‑Johnson syndrome), eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvac‑ cinal...reported health outcomes, including mental and physical functioning , cardiovascular diseases, and auto- immune disorders, were found. These findings...words: smallpox vaccine, questionnaires, military medicine , longitudinal studies, chronic disease, quality of life [Human Vaccines 4:2, 127‑133; March

TLR3 and TLR9 agonists improve postexposure vaccination efficacy of live smallpox vaccines.

PubMed

Israely, Tomer; Melamed, Sharon; Achdout, Hagit; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination.

TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

PubMed Central

Israely, Tomer; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

2014-01-01

Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination. PMID:25350003

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

The XIX century smallpox prevention in Naples and the risk of transmission of human blood-related pathogens.

PubMed

Buonaguro, Franco Maria; Tornesello, Maria Lina; Buonaguro, Luigi

2015-01-27

Vaccines are the most successful strategy developed in Medicine to prevent and even eradicate the most dreadful epidemic infectious diseases. The history of smallpox vaccination in Naples is quite unique. Although Galbiati established the retro-vaccination (1803) and developed the "calf" lymph vaccine, recognized and implemented since 1864 as the optimal smallpox vaccine in the following hundred years, Naples general population was mainly vaccinated with "human" lymph from abandoned children until 1893. Mini-epidemics of syphilis and serum hepatitis were periodically reported as results of arm-to-arm procedure. The risk of transmission of blood-related pathogens was higher in Naples where >80% of abandoned children, used as repository of cowpox virus, were dying in their first year of life. Recent vaccinology standards finally eliminated the risk of adventitious contaminating pathogens. Implementation of hepatitis B vaccination since 1991 eventually contributed to current HBV prevalence in Campania region <1%, within the range of the European Countries.

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.80 - Calculation of medical benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

42 CFR 102.2 - Summary of available benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Summary of available benefits. 102.2 Section 102.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... smallpox vaccine recipient or vaccinia contact was the direct result of a covered injury, as described in...

Governments, off-patent vaccines, smallpox and universal childhood vaccination.

PubMed

Music, Stanley

2010-01-22

WHO is now celebrating more than 30 years of freedom from smallpox. What was originally seen as a victory over an ancient scourge can now be viewed as an epidemiologically driven programme to overcome governmental inertia and under-achievement in delivering an off-patent vaccine. Though efforts are accelerating global vaccine use, a plea is made to push the world's governments to commit to universal childhood vaccination via a proposed new programme. The latter should begin by exploiting a long list of ever more affordable off-patent vaccines, vaccines that can virtually eliminate the bulk of the world's current vaccine-preventable disease burden.

The new cell culture smallpox vaccine should be offered to the general population.

PubMed

Bicknell, William; James, Kenneth

2003-01-01

A series of major factors must be weighed in deciding whether or not, and to what extent, a particular country should consider pre-exposure vaccination for smallpox. These include the risk of a bioterrorist attack using smallpox, the risk of secondary spread from another country, the risks and benefits of vaccination, the effectivenes s of vaccination pre- and post-exposure, the prevalence of immunocompromised persons, the capacity of the medical care delivery system and the wealth of a nation. We review here the issues and variables relevant for policy making, propose a framework for country-specific decision making and suggest the World Health Organization has a key role to play, particularly with regard to lower-income countries. In doing so, we support the proposition. Copyright 2003 John Wiley & Sons, Ltd.

Evaluation of smallpox vaccines using variola neutralization

PubMed Central

Damon, Inger K.; Davidson, Whitni B.; Hughes, Christine M.; Olson, Victoria A.; Smith, Scott K.; Holman, Robert C.; Frey, Sharon E.; Newman, Frances; Belshe, Robert B.; Yan, Lihan; Karem, Kevin

2009-01-01

The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific ‘in vitro’ activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination. PMID:19339477

Smallpox manifestations and survival during the Boston epidemic of 1901 to 1903.

PubMed

Albert, Michael R; Ostheimer, Kristen G; Liewehr, David J; Steinberg, Seth M; Breman, Joel G

2002-12-17

Clinical records of 243 patients with smallpox consecutively admitted to the Southampton Street smallpox hospital in Boston, Massachusetts, during the 1901-1903 epidemic were reviewed. Smallpox was divided into five categories of varying severity; 47% of patients had varioloid, a relatively mild form of the disease usually occurring in previously vaccinated individuals with incomplete immunity. Survival information is available for 206 patients, of whom 36 (17.5%) died. Vaccination status, disease severity, and age were associated with survival, whereas sex, birthplace, and race were not. While full recovery often took weeks, most deaths occurred 7 to 14 days after the onset of symptoms, and all deaths occurred within 18 days of symptom onset. Smallpox was eradicated worldwide in 1977, but knowledge of the disease is essential because its cause, variola virus, is considered a potential biological weapon.

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

PubMed Central

Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2015-01-01

Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

EFFECTS OF X RADIATION ON THE REPRODUCTION OF SMALLPOX VACCINE VIRUS IN TISSUE CULTURE (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamalyan, L.A.; Ter-Pogosyan, R.A.

1963-01-01

Infectious and hemagglutinic properties of smallpox vaccine virus in chick embryo cutaneous-muscular tissue irradiated with 20-kr of x radiation were investigated. It was found that the radiation induced increased virus reproduction. Accumulation of hemagglutinin did not differ in irradiated and nonirradiated cultures. (R.V.J.)

Public Health and Medicine in the Chinese People’s Republic.

DTIC Science & Technology

1960-10-31

2,5 The fight against smallpox in the Homindan period was very poorly organised^ although the effective method of vaccination h&d been in human...compulsory vaccination of ! " - . ■ ■ ■ ■ - :’the population with the aim of complete elimination of cases of nnallpo?< r- f...the introduction of compulsory free vaccination \\ i nr-toral smallpox has been completely sliadcafced iri all provinces» i ’ | cities and villages

A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE®

PubMed Central

von Krempelhuber, Alfred; Vollmar, Jens; Pokorny, Rolf; Rapp, Petra; Wulff, Niels; Petzold, Barbara; Handley, Amanda; Mateo, Lyn; Siersbol, Henriette; Kollaritsch, Herwig; Chaplin, Paul

2009-01-01

IMVAMUNE® is a Modified Vaccinia Ankara-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE® in 164 healthy volunteers. All three IMVAMUNE® doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1×108 TCID50 IMVAMUNE® dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE® dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine. PMID:19944151

Neurologic adverse events associated with smallpox vaccination in the United States – response and comment on reporting of headaches as adverse events after smallpox vaccination among military and civilian personnel

PubMed Central

Schumm, Walter R

2006-01-01

Background Accurate reporting of adverse events occurring after vaccination is an important component of determining risk-benefit ratios for vaccinations. Controversy has developed over alleged underreporting of adverse events within U.S. military samples. This report examines the accuracy of adverse event rates recently published for headaches, and examines the issue of underreporting of headaches as a function of civilian or military sources and as a function of passive versus active surveillance. Methods A report by Sejvar et al was examined closely for accuracy with respect to the reporting of neurologic adverse events associated with smallpox vaccination in the United States. Rates for headaches were reported by several scholarly sources, in addition to Sejvar et al, permitting a comparison of reporting rates as a function of source and type of surveillance. Results Several major errors or omissions were identified in Sejvar et al. The count of civilian subjects vaccinated and the totals of both civilians and military personnel vaccinated were reported incorrectly by Sejvar et al. Counts of headaches reported in VAERS were lower (n = 95) for Sejvar et al than for Casey et al (n = 111) even though the former allegedly used 665,000 subjects while the latter used fewer than 40,000 subjects, with both using approximately the same civilian sources. Consequently, rates of nearly 20 neurologic adverse events reported by Sejvar et al were also incorrectly calculated. Underreporting of headaches after smallpox vaccination appears to increase for military samples and for passive adverse event reporting systems. Conclusion Until revised or corrected, the rates of neurologic adverse events after smallpox vaccinated reported by Sejvar et al must be deemed invalid. The concept of determining overall rates of adverse events by combining small civilian samples with large military samples appears to be invalid. Reports of headaches as adverse events after smallpox vaccination appear to be have occurred much less frequently using passive surveillance systems and by members of the U.S. military compared to civilians, especially those employed in healthcare occupations. Such concerns impact risk-benefit ratios associated with vaccines and weigh against making vaccinations mandatory, without informed consent, even among military members. Because of the issues raised here, adverse event rates derived solely or primarily from U.S. Department of Defense reporting systems, especially passive surveillance systems, should not be used, given better alternatives, for making public health policy decisions. PMID:17096855

Army Medical Department Support to Stability Operations

DTIC Science & Technology

2007-02-28

eliminate bubonic plague , vaccinate against smallpox, and institute measures for a safe water supply.21 Lieutenant General Arthur MacArthur, military...the war.36 Though the many medical assistance programs were plagued with unending challenges, and the overall outcome of the war has yet to be

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.91 - Secretary's review authority.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Secretary's review authority. 102.91 Section 102.91 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's Determinations § 102.91 Secretary's review authority...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.22-102.29 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false [Reserved] 102.22-102.29 Section 102.22-102.29 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Covered Injuries §§ 102.22-102.29 [Reserved] ...

42 CFR 102.74 - Disapproval of benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Disapproval of benefits. 102.74 Section 102.74 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.74 Disapproval of benefits. (a) If the Secretary...

Metabolites as Biomarkers of Adverse Reactions Following Vaccination: A Pilot Study using Nuclear Magnetic Resonance Metabolomics

PubMed Central

McClenathan, Bruce M.; Stewart, Delisha A.; Spooner, Christina E.; Pathmasiri, Wimal W.; Burgess, Jason P.; McRitchie, Susan L.; Choi, Y. Sammy; Sumner, Susan C.J.

2017-01-01

An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. PMID:28169076

Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics.

PubMed

McClenathan, Bruce M; Stewart, Delisha A; Spooner, Christina E; Pathmasiri, Wimal W; Burgess, Jason P; McRitchie, Susan L; Choi, Y Sammy; Sumner, Susan C J

2017-03-01

An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1 H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers. Published by Elsevier Ltd.

Smallpox vaccination and adverse reactions. Guidance for clinicians.

PubMed

Cono, Joanne; Casey, Christine G; Bell, David M

2003-02-21

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.

Smallpox-Related Knowledge and Beliefs among Recent College Graduates

ERIC Educational Resources Information Center

Bungum, Timothy; Day, Charlene

2006-01-01

Recent world events have increased concern and preparations for possible bioterror events. Despite worldwide efforts to limit access to bio-weapons, smallpox is still considered a potential bioterror threat. Americans' understanding of smallpox could prevent panic and enhance the willingness of citizens to receive vaccinations. Objective: The…

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.44 - Representatives of requesters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.72 - Sufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Sufficient documentation for eligibility and benefits determinations. 102.72 Section 102.72 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.72...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.43 - Deadlines for submitting documentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Deadlines for submitting documentation. 102.43 Section 102.43 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.43 Deadlines for submitting...

42 CFR 102.71 - Insufficient documentation for eligibility and benefits determinations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Insufficient documentation for eligibility and benefits determinations. 102.71 Section 102.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.71...

42 CFR 102.73 - Approval of benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Approval of benefits. 102.73 Section 102.73 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that...

The Royal Philanthropic Expedition of the Vaccine: a landmark in the history of public health.

PubMed

Soto-Pérez-de-Celis, E

2008-11-01

In 1979, smallpox officially became the first disease ever to be eradicated by mankind. The global efforts to defeat this dreadful pandemic, however, started almost two centuries before. One of the most important, and sometimes forgotten, events in the fight against smallpox was the Royal Philanthropic Expedition of the Vaccine, commissioned by Charles IV of Spain to physicians Francisco Xavier Balmis y Berenguer and Jose Salvany in 1804. The aim of this expedition was to take the smallpox vaccine, discovered by Jenner, to Spain's territories in the Americas and in the Far East. After several years of vaccination in modern day Puerto Rico, Cuba, Venezuela, Ecuador, Peru, Bolivia, Chile, Mexico and the Philippines, the expedition returned to Europe. To this day, the Balmis and Salvany expedition remains a great example of international cooperation, and a landmark in the history of public health.

Insights into human CD8(+) T-cell memory using the yellow fever and smallpox vaccines.

PubMed

Ahmed, Rafi; Akondy, Rama S

2011-03-01

Live virus vaccines provide a unique opportunity to study human CD8(+) T-cell memory in the context of a controlled, primary acute viral infection. Yellow fever virus-17D and Dryvax are two such live-virus vaccines that are highly efficacious, used worldwide and provide long-term immunity against yellow fever and smallpox respectively. In this review, we describe the properties of virus-specific memory CD8(+) T cells generated in smallpox and yellow fever vaccinees. We address fundamental questions regarding magnitude, functional quality and longevity of the CD8(+) T-cell response, which are otherwise challenging to address in humans. These findings provide insights into the attributes of the human immune system as well as provide a benchmark for the optimal quality of a CD8(+) T-cell response that can be used to evaluate novel candidate vaccines.

Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

PubMed Central

Rice, Amanda D.; Adams, Mathew M.; Lampert, Bernhard; Foster, Scott; Lanier, Randall; Robertson, Alice; Painter, George; Moyer, Richard W.

2011-01-01

CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination. PMID:21369346

Medical statistics and hospital medicine: the case of the smallpox vaccination.

PubMed

Rusnock, Andrea

2007-01-01

Between 1799 and 1806, trials of vaccination to determine its safety and efficacy were undertaken in hospitals in London, Paris, Vienna, and Boston. These trials were among the first instances of formal hospital evaluations of a medical procedure and signal a growing acceptance of a relatively new approach to medical practice. These early evaluations of smallpox vaccination also relied on descriptive and quantitative accounts, as well as probabilistic analyses, and thus occupy a significant, yet hitherto unexamined, place in the history of medical statistics.

The Smallpox Threat: The School Nurse's Role

ERIC Educational Resources Information Center

Martin, Mary E.; Didion, Judy

2003-01-01

Today, with the threat of bioterrorism and war, there is a new dimension to the traditional role of the school nurse. The smallpox threat to public health will invoke the school nurse's role as an educator, liaison, and consultant in the community. This article discusses smallpox, the vaccination process, adverse effects, and postvaccination care.…

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Calculation and Payment of Benefits § 102.83 Payment of all benefits. (a) The Secretary...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

42 CFR 102.60 - Documentation an eligible requester seeking medical benefits must submit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation an eligible requester seeking medical benefits must submit. 102.60 Section 102.60 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Required Documentation for Eligible Requesters To...

A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost

PubMed Central

Xiao, Yuhong; Aldaz-Carroll, Lydia; Ortiz, Alexandra M.; Whitbeck, J. Charles; Alexander, Edward; Lou, Huan; Davis, J. Heather L.; Braciale, Thomas J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Isaacs, Stuart N.

2007-01-01

The heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. While subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. Here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. Mice vaccinated with vaccinia virus envelope proteins from the mature virus (MV) and extracellular virus (EV) adjuvanted with CpG-ODN and alum were protected from lethal intranasal challenge with vaccinia virus and the mouse-specific ectromelia virus. Organs from mice vaccinated with three proteins (A33, B5 and L1) and then sacrificed after challenge contained significantly lower titers of virus when compared to control groups of mice that were not vaccinated or that received sub-optimal formulations of the vaccine. Sera from groups of mice obtained prior to challenge had neutralizing activity against the MV and also inhibited comet formation indicating anti-EV activity. Long-term partial protection was also seen in mice challenged with vaccinia virus 6 months after initial vaccinations. Thus, this work represents a step toward the development of a practical subunit smallpox vaccine. PMID:17098336

[Smallpox virus as biological weapon].

PubMed

Kondrusik, Maciej; Hermanowska-Szpakowicz, Teresa

2003-02-01

Smallpox, because of its high case-fatality rate, easy transmission from human to human, lack of specific treatment represents nowadays one of the main threats in bioterrorist attacks. Over the centuries, naturally occurring smallpox with its case-fatality over 30 percent and its ability to spread in any climate and season has been treated as the most dangerous infectious disease. But it is now, 25 years after the last documented case of smallpox and cessation of routine vaccination in present mobile and susceptible population, smallpox virus spread might be rapid and devastating.

Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines

PubMed Central

Drexler, Ingo; Staib, Caroline; Kastenmüller, Wolfgang; Stevanović, Stefan; Schmidt, Burkhard; Lemonnier, François A.; Rammensee, Hans-Georg; Busch, Dirk H.; Bernhard, Helga; Erfle, Volker; Sutter, Gerd

2003-01-01

Despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. New, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8+ T cells and conserved among Orthopoxvirus species including variola virus. This finding has permitted analysis and monitoring of epitope-specific T cell responses after immunization and demonstration of the identified T cell specificity in an A*0201-positive human donor. Vaccination of transgenic mice allowed us to compare the immunogenicity of several vaccinia viruses including highly attenuated, replication-deficient modified vaccinia virus Ankara (MVA). MVA vaccines elicited levels of CD8+ T cell responses that were comparable to those induced by the replication-competent vaccinia virus strains. Finally, we demonstrate that MVA vaccination is fully protective against a lethal respiratory challenge with virulent vaccinia virus strain Western Reserve. Our data provide a basis to rationally estimate immunogenicity of safe, second-generation poxvirus vaccines and suggest that MVA may be a suitable candidate. PMID:12518065

In vitro efficacy of ST246 against smallpox and monkeypox.

PubMed

Smith, Scott K; Olson, Victoria A; Karem, Kevin L; Jordan, Robert; Hruby, Dennis E; Damon, Inger K

2009-03-01

Since the eradication of smallpox and the cessation of routine childhood vaccination for smallpox, the proportion of the world's population susceptible to infection with orthopoxviruses, such as variola virus (the causative agent of smallpox) and monkeypox virus, has grown substantially. In the United States, the only vaccines for smallpox licensed by the Food and Drug Administration (FDA) have been live virus vaccines. Unfortunately, a substantial number of people cannot receive live virus vaccines due to contraindications. Furthermore, no antiviral drugs have been fully approved by the FDA for the prevention or treatment of orthopoxvirus infection. Here, we show the inhibitory effect of one new antiviral compound, ST-246, on the in vitro growth properties of six variola virus strains and seven monkeypox virus strains. We performed multiple assays to monitor the cytopathic effect and to evaluate the reduction of viral progeny production and release in the presence of the compound. ST-246 had 50% effective concentrations of

Progression of pathogenic events in cynomolgus macaques infected with variola virus.

PubMed

Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

[Lessons learnt from the German smallpox outbreaks after World War II].

PubMed

Sasse, Julia; Gelderblom, Hans R

2015-07-01

Even though smallpox was declared eradicated by WHO in 1980, it cannot be ruled out that the etiological variola virus could be used as a biological weapon. Undestroyed viruses from biowarfare programmes, virus strains left undetected in a freezer or dangerous recombinant poxvirus constructs could cause dangerous outbreaks in a relatively unprotected population. Despite an abundance of studies performed during the eradication of smallpox, epidemiological data for preparedness planning and outbreak control in modern, industrialized countries are scarce. Full-text hand search for the period from 1945 to 1975 in the main German public health journals. After World War II 12 smallpox outbreaks occurred in Germany. They were studied with the focus on the period of contagiousness, the protective effect of vaccination, booster-effect of revaccination and the place of infection. A total of 95 individuals contracted smallpox, including 10 fatalities. Despite having been previously vaccinated, 81 vaccinated persons came down with smallpox, yet 91% of them developed only mild symptoms. These patients presented a high risk for spreading the infection to contact persons due to misinterpretation of symptoms and the continuing social contacts. Basically, the risk of transmission in the first 2 to 3 days after onset of symptoms was low, thus facilitating antiepidemic measures. The importance of hospital preparedness is emphasized by the fact that most infections occurred in hospitals. The data analyzed provide valuable information for today's outbreak response planning and counter bioterrorism preparedness.

Vaccination and allergy.

PubMed

Rottem, Menachem; Shoenfeld, Yehuda

2004-06-01

Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks. Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations. Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.92 - No additional judicial or administrative review of determinations made under this part.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false No additional judicial or administrative review of determinations made under this part. 102.92 Section 102.92 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Reconsideration of the Secretary's...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

42 CFR 102.70 - Determinations the Secretary must make before benefits can be paid.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Determinations the Secretary must make before benefits can be paid. 102.70 Section 102.70 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Secretarial Determinations § 102.70 Determinations...

Host range, growth property, and virulence of the smallpox vaccine: Vaccinia virus Tian Tan strain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang Qing; Yang Lin; Zhu Weijun

2005-05-10

Vaccinia Tian Tan (VTT) was used as a vaccine against smallpox in China for millions of people before 1980, yet the biological characteristics of the virus remain unclear. We have characterized VTT with respect to its host cell range, growth properties in vitro, and virulence in vivo. We found that 11 of the 12 mammalian cell lines studied are permissive to VTT infection whereas one, CHO-K1, is non-permissive. Using electron microscopy and sequence analysis, we found that the restriction of VTT replication in CHO-K1 is at a step before viral maturation probably due to the loss of the V025 gene.more » Moreover, VTT is significantly less virulent than vaccinia WR but remains neurovirulent in mice and causes significant body weight loss after intranasal inoculation. Our data demonstrate the need for further attenuation of VTT to serve either as a safer smallpox vaccine or as a live vaccine vector for other pathogens.« less

The Bug Stops Here: Force Protection and Emerging Infectious Diseases

DTIC Science & Technology

2005-11-01

said in 1972 that “the future of infectious diseases will be very dull.” Successful vaccines against smallpox and polio only furthered belief that...probably higher. Mounting evidence implicates microbes in heart disease, rheumatoid arthritis, diabetes, multiple sclerosis, autism , chronic lung diseases...cross protection against smallpox. Louis Pasteur later adopted the word ‘ vaccination ’ for immunization against any disease. 19 “History of Military

Smallpox Vaccination is Not Associated with Infertility in a Healthy Young Adult Population

DTIC Science & Technology

2008-06-01

Naval Health Research Center Smallpox Vaccination is Not Associated with Infertility in A Healthy Young Adult Population I. G. Jacobson G. R...pregnant.34-37 Concerns exist regarding reproductive health , including potential infertility, among young adults with military-related occupational...Gumbs C. J. Sevick T. C. Smith M. A.K. Ryan Report No. 07-27 Approved for public release: distribution is unlimited. Naval Health

Prediction of Steps in the Evolution of Variola Virus Host Range

PubMed Central

Smithson, Chad; Purdy, Alex; Verster, Adrian J.; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox. PMID:24626337

Prediction of steps in the evolution of variola virus host range.

PubMed

Smithson, Chad; Purdy, Alex; Verster, Adrian J; Upton, Chris

2014-01-01

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.

75 FR 3244 - Prospective Grant of Exclusive License: Monoclonal Antibodies Against Smallpox/Orthopoxviruses

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... safe and effective for prevention of smallpox, it is well documented that various adverse reactions in...) prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia...

[The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803].

PubMed

Rigau-Pérez, José G

2004-09-01

Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000(®) compared with Dryvax(®).

PubMed

Tack, Danielle M; Karem, Kevin L; Montgomery, Jay R; Collins, Limone; Bryant-Genevier, Marthe G; Tiernan, Rosemary; Cano, Maria; Lewis, Paige; Engler, Renata J M; Damon, Inger K; Reynolds, Mary G

2013-07-01

Routine vaccination against smallpox (variola) ceased in the US in 1976. However, in 2002 limited coverage for military personnel and some healthcare workers was reinstituted. In March 2008, ACAM2000® replaced Dryvax® as the vaccine used in the United States against smallpox. Unintentional transfer of vaccinia virus from a vaccination site by autoinoculation or contact transmission, can have significant public health implications. We summarize unintentional virus transfer AEs associated with ACAM2000® since March 2008 and compare with Dryvax®. We identified 309 reports for ACAM2000® with skin or ocular involvement, of which 93 were autoinoculation cases and 20 were contact transmission cases. The rate for reported cases of autoinoculation was 20.6 per 100,000 vaccinations and for contact transmission was 4.4 per 100,000 vaccinations. Eighteen contact transmission cases could be attributed to contact during a sporting activity (45%) or intimate contact (45%). Of the 113 unintentional transfer cases, 6 met the case definition for ocular vaccinia. The most common locations for all autoinoculation and contact cases were arm/elbow/shoulder (35/113; 31%) and face (24/113; 21%). Methods We reviewed 753 reports associated with smallpox in the Vaccine Adverse Event Reporting System and CDC Poxvirus consultation log, reported from March 2008 to August 2010. Reports were classified into categories based upon standard case definitions. Overall, unintentional transfer events for ACAM2000® and Dryvax® are similar. We recommend continued efforts to prevent transfer events and continuing education for healthcare providers focused on recognition of vaccinia lesions, proper sample collection, and laboratory testing to confirm diagnosis.

Assessment of the Protective Effect of Imvamune and Acam2000 Vaccines against Aerosolized Monkeypox Virus in Cynomolgus Macaques

PubMed Central

Graham, Victoria A.; Bewley, Kevin R.; Dennis, Mike; Taylor, Irene; Funnell, Simon G. P.; Bate, Simon R.; Steeds, Kimberley; Tipton, Thomas; Bean, Thomas; Hudson, Laura; Atkinson, Deborah J.; McLuckie, Gemma; Charlwood, Melanie; Roberts, Allen D. G.; Vipond, Julia

2013-01-01

To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies. PMID:23658452

Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus

PubMed Central

Rubins, Kathleen H.; Huggins, John W.; Fisher, Robert W.; Johnson, Anthony J.; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E.; Jahrling, Peter B.

2011-01-01

Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections – an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions. PMID:21998632

RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

PubMed

MEYER, H M; HOSTETLER, D D; BERNHEIN, B C; ROGERS, N G; LAMBIN, P; CHASSARY, A; LABUSQUIERE, R; SMADEL, J E

1964-01-01

An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

[History of vaccination: from empiricism towards recombinant vaccines].

PubMed

Guérin, N

2007-01-01

Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

Immunization safety in US print media, 1995-2005.

PubMed

Hussain, Hamidah; Omer, Saad B; Manganello, Jennifer A; Kromm, Elizabeth Edsall; Carter, Terrell C; Kan, Lilly; Stokley, Shannon; Halsey, Neal A; Salmon, Daniel A

2011-05-01

To identify and describe vaccine safety in US newspaper articles. Articles (1147) from 44 states and Washington, DC, between January 1, 1995, and July 15, 2005, were identified by using the search terms "immunize or vaccine" and "adverse events or safety or exemption or danger or risk or damage or injury or side effect" and were coded by using a standardized data-collection instrument. The mean number of vaccine-safety articles per state was 26. Six (not mutually exclusive) topics were identified: vaccine-safety concerns (46%); vaccine policy (44%); vaccines are safe (20%); immunizations are required (10%); immunizations are not required (8%); and state/school exemption (8%). Three spikes in the number of newspaper articles about vaccine-safety issues were observed: in 1999 regarding rotavirus vaccine and in 2002 and 2003 regarding smallpox vaccine. Excluding articles that referred to rotavirus and smallpox vaccines, 37% of the articles had a negative take-home message. Ongoing monitoring of news on vaccine safety may help the content and framing of vaccine-safety messages.

Countermeasures to the bioterrorist threat of smallpox.

PubMed

Jahrling, Peter B; Fritz, Elizabeth A; Hensley, Lisa E

2005-12-01

Variola, the agent of smallpox, is a bioterrorist threat, as is monkeypox virus, which also occurs naturally in Africa. Development of countermeasures, in the form of improved vaccines, antiviral drugs, and other therapeutic strategies are a high priority. Recent advances in molecular biology and in animal model development have provided fresh insight into the virulence determinants for smallpox and the pathophysiology of disease. The complex replication cycle for orthopoxviruses, and the pivotal role for viral-specific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The "toxemia" of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent "black" smallpox. This suggests a potential role for therapeutic strategies developed for septic shock, in treatment of smallpox. Drugs licensed for other viruses which share molecular targets with orthopoxviruses (e.g. Cidofovir) or cancer drugs (e.g. Gleevec and other tyrosine kinase inhibitors) have immediate application for treatment of smallpox and monkeypox and provide leads for second generation drugs with higher therapeutic indices. Recent advances in identification of virulence determinants and immune evasion genes facilitate the design of alternative vaccines to replace live vaccinia strains that are unsuitable for a large proportion of individuals in a mass immunization campaign.

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, Philippe; Tegnell, Anders; Baka, Agoritsa; Van Loock, Frank; Hendriks, J; Werner, Albrecht; Maidhof, Heinrich; Gouvras, Georgios

2004-12-15

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Bichat guidelines for the clinical management of smallpox and bioterrorism-related smallpox.

PubMed

Bossi, P; Tegnell, A; Baka, A; van Loock, F; Werner, A; Hendriks, J; Maidhof, H; Gouvras, G

2004-12-01

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

[Marked on the skin: vaccination and smallpox in Argentina (1870-1910)].

PubMed

Di Liscia, Maria Silvia

2011-02-01

This paper studies the smallpox vaccination in Argentina since 1870, when these discussions were initiated until the 1910s, when they were extended to the rest of the country. We analyze immunization practices implemented prior to the compulsory vaccination law, passed in 1886 for the Capital and in 1904 for the rest of the country. Such a move found resistance from different sectors. Its approval depended on the consequences of modernization and urbanization, the weight of hygienists in the political arena, and its extension depended on a different administrative conception, incorporating new areas and sectors to the national scenario.

Smallpox infections during pregnancy, lessons on pathogenesis from nonpregnant animal models of infection.

PubMed

Hassett, Daniel E

2003-10-01

Both vaccinated and unvaccinated women during pregnancy who contract variola virus, the causative agent of smallpox, suffer much higher mortality rates than nonpregnants. Furthermore, acute maternal smallpox leads to spontaneous abortion, premature termination of pregnancy and early postnatal infant mortality. The mechanisms governing the abortifacient activity of smallpox, as well as the enhanced susceptibility of gestating women to lethal disease, have remained largely unexamined. Experimental poxvirus infections in nonpregnant small animal models have revealed that T helper type 1 (TH1) cytokines promote efficient resolution of these infections whereas type 2 (TH2) cytokines enhance viral pathogenesis. These data, combined with recent understanding of how the immune system is modulated by pregnancy, may offer important clues as to the increased pathogenesis of variola in pregnant women. The aim of this review is to bring together the current literature on the effects of poxvirus infections in nonpregnant hosts, as well as the effects of pregnancy on the immune system, in order to develop unifying concepts that may provide insight into the pathogenesis of variola during pregnancy and why prior vaccination with vaccinia virus the live anti-variola vaccine offers less protection to pregnant women and their unborn children.

Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines.

PubMed

Tscharke, David C; Karupiah, Gunasegaran; Zhou, Jie; Palmore, Tara; Irvine, Kari R; Haeryfar, S M Mansour; Williams, Shanicka; Sidney, John; Sette, Alessandro; Bennink, Jack R; Yewdell, Jonathan W

2005-01-03

The large size of poxvirus genomes has stymied attempts to identify determinants recognized by CD8+ T cells and greatly impeded development of mouse smallpox vaccination models. Here, we use a vaccinia virus (VACV) expression library containing each of the predicted 258 open reading frames to identify five peptide determinants that account for approximately half of the VACV-specific CD8+ T cell response in C57BL/6 mice. We show that the primary immunodominance hierarchy is greatly affected by the route of VACV infection and the poxvirus strain used. Modified vaccinia virus ankara (MVA), a candidate replacement smallpox vaccine, failed to induce responses to two of the defined determinants. This could not be predicted by genomic comparison of viruses and is not due strictly to limited MVA replication in mice. Several determinants are immunogenic in cowpox and ectromelia (mousepox) virus infections, and immunization with the immunodominant determinant provided significant protection against lethal mousepox. These findings have important implications for understanding poxvirus immunity in animal models and bench-marking immune responses to poxvirus vaccines in humans.

The rediscovery of smallpox.

PubMed

Thèves, C; Biagini, P; Crubézy, E

2014-03-01

Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts--variolation, quarantine, and the isolation of infected subjects--until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Genital Autoinoculation with Vaccinia: A Look at Two Cases.

PubMed

Whittington, Julie R; Rollene, Nanette L; Gist, Richard S

2018-05-01

Smallpox, or vaccinia, has been eradicated worldwide as a disease; however, it may be weaponized and is thus a required immunization when military members deploy to certain parts of the world. We report two unusual cases of genital autoinoculation following smallpox vaccination. Both patients' lesions resolved without sequelae within 20 d. We advocate for thorough education on this potential vaccination adverse event. These cases highlight the importance of a broad differential diagnosis when dealing with vulvar lesions, particularly in our military population.

Inoculating for smallpox.

PubMed

Greene, Jan

2003-04-01

In California, one hospital decided the time was right to inoculate staff volunteers with the smallpox vaccine. Weighing the same pros and cons--civic responsibility, health risk, cost and reluctance of staff--other hospitals opted out of inoculations, at least for now. What led these organizations to such divergent decisions?

[Treatment and remedies against smallpox outbreaks in Ferrara in the late nineteenth century].

PubMed

Vicentini, Chiara Beatrice; Manfredini, Stefano; Altieri, Lorenzo; Lupi, Silvia; Guidi, Enrica; Contini, Carlo

2013-09-01

Health interventions against smallpox during the two epidemics in the second half of the 19th century are outlined. The 1871 hospital health report and the medical report on smallpox patients treated at the hospital and poorhouse of Ferrara between January 1891 and January 1892, drawn up by Alessandro Bennati, provide both interesting data and insights into the treatments and remedies of the time. The treatment of this illness was - and indeed could be - nothing other than symptomatic, there being no real means to halt the spread of the disease. Rather, other remedies were found by alleviating pain and regaining energy during the various stages of the disease. A close relationship between vaccination and the incidence and gravity of the illness is underlined. When the practice of vaccination started to be widely employed at the end of the century, there were almost no cases of death due to smallpox. The pharmacopoeias of the time, Antonio Campana's Farmacopea ferrarese in particular, proved an essential guide in the analysis of each document.

ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense.

PubMed

Monath, Thomas P; Caldwell, Joseph R; Mundt, Wolfgang; Fusco, Joan; Johnson, Casey S; Buller, Mark; Liu, Jian; Gardner, Bridget; Downing, Greg; Blum, Paul S; Kemp, Tracy; Nichols, Richard; Weltzin, Richard

2004-10-01

The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax.

Assessment of vaccination coverage, vaccination scar rates, and smallpox scarring in five areas of West Africa.

PubMed

Henderson, R H; Davis, H; Eddins, D L; Foege, W H

1973-01-01

In 1966, nineteen countries of West and Central Africa began a regional smallpox eradication and measles control programme in cooperation with the World Health Organization. This paper summarizes sample survey data collected to assess the results of the programme in Northern Nigeria (Sokoto and Katsina Provinces), Western Nigeria, Niger, Dahomey, and Togo. These data indicate that the programme, which used mass vaccination campaigns based on a collecting-point strategy, was generally successful in reaching a high proportion of the population. Analysis of vaccination coverage and vaccination scar rates by age underlined the importance to the programme of newborn children who accumulate rapidly following the mass campaign. Of all persons without vaccination scars at the time of the surveys, 34.4% were under 5 years of age; in the absence of a maintenance programme, this figure would rise to 40% after 1 year.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

PubMed

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

PubMed Central

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. PMID:29403503

Expanding the histologic findings in smallpox-related post-vaccinial non-viral folliculitis.

PubMed

Bunick, Christopher G; Mariwalla, Kavita; Ibrahim, Omer; Modi, Badri; Imaeda, Suguru; McNiff, Jennifer M

2013-03-01

Post-vaccinial non-viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to smallpox vaccination. Contrary to more serious smallpox vaccine reactions, post-vaccinial non-viral folliculitis has a benign course and resolves spontaneously within approximately 7 days. We describe additional histopathologic findings associated with post-vaccinial non-viral folliculitis, which has only been described once previously. New findings include the presence of a neutrophilic or lymphohistiocytic infiltrate that is concentrated around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind post-vaccinial non-viral folliculitis. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

An examination of John Fewster's role in the discovery of smallpox vaccination.

PubMed

Thurston, L; Williams, G

2015-01-01

Edward Jenner is recognised today as the father of vaccination but, as this paper explores, he was not the only Gloucestershire doctor to be linked to this discovery. John Fewster, a local surgeon and apothecary, is also said to have experimented with vaccination, many years before Jenner. This claim is made in a letter addressed to John Coakley Lettsom, written by John Player, a Quaker farmer. Player describes in detail Fewster's realisation that cowpox could be used to protect against smallpox. This letter is frequently cited but has not previously been subjected to critical analysis. We have identified several inconsistencies, including conflicting dates and a possible ulterior motive in that Player's son was to marry Fewster's daughter. We think it unlikely that Player, a devout Quaker, would have consciously fabricated evidence, but argue that the discrepancies in his account undermine the assumption that Fewster carried out vaccination experiments prior to Jenner. We also explore the assertion that Fewster presented a paper in 1765 on the subject of cowpox and its protective effect over smallpox. We conclude that, although there is no doubt that Fewster did pre-empt Jenner's discovery of vaccination, he did not realise the significance or importance of this momentous medical advance.

Vaccines Through Centuries: Major Cornerstones of Global Health

PubMed Central

Hajj Hussein, Inaya; Chams, Nour; Chams, Sana; El Sayegh, Skye; Badran, Reina; Raad, Mohamad; Gerges-Geagea, Alice; Leone, Angelo; Jurjus, Abdo

2015-01-01

Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history. PMID:26636066

[Relation of vaccination to childhood malignancy].

PubMed

Neumann, G

1980-01-18

74 German legitimate children who have died 1972/73 by a malignant neoplasm did not differ significantly from healthy controls by their vaccination history. This holds true for vaccination against tetanus, poliomyelitis, smallpox, and tuberculosis. By BCG-vaccination neither a promoting nor a protecting effect could be discovered. Controls were more often vaccinated against diphtheria than cases.

Safeguarding slaves: smallpox, vaccination, and governmental health policies among the enslaved population in the Danish West Indies, 1803-1848.

PubMed

Jensen, Niklas Thode

2009-01-01

During the first half of the nineteenth century, a unique system of vaccination against smallpox was developed in the island of St. Croix in the Danish West Indies. The primary intention was to protect the population of enslaved workers, which was of fundamental importance to the economy of the colony. However, because the Danish abolition of the slave trade in 1803 had stopped the imports of new enslaved workers from Africa, the population was also decreasing. The vaccination system's success was due to a high degree of governmental control of the enslaved population that was virtually unseen anywhere else in the Caribbean.

76 FR 28991 - Privacy Act of 1974; Report of a New System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... pandemic 2009 H1N1 influenza vaccines, antiviral medications (e.g., Tamiflu), anthrax vaccines, and smallpox vaccines. The PREP Act directs the Secretary to establish administrative procedures to compensate... resulting from pandemic, epidemic, or security countermeasures such as vaccines identified in declarations...

[The historical development of immunization in Germany. From compulsory smallpox vaccination to a National Action Plan on Immunization].

PubMed

Klein, S; Schöneberg, I; Krause, G

2012-11-01

In the German Reich, smallpox vaccinations were organized by the state. A mandatory vaccination throughout the empire was introduced in 1874, which was continued in the Federal Republic of Germany (FRG) and the German Democratic Republic (GDR) until 1982/1983. From 1935, health departments were responsible for vaccinations. In the GDR, immunization was tightly organized: The state made great efforts to achieve high vaccination rates. Responsibilities were clearly defined at all levels and for all ages. While vaccination was initially mandatory only at the regional level, the legally mandated immunization schedule later contained compulsory vaccinations, e.g., against measles. In the beginning there were mandatory vaccinations in the FRG at the Länder level. Since 1961, the Federal Epidemics Act has impeded obligatory vaccinations. Instead, voluntary vaccinations based on recommendations were stressed. Since the 1980s, vaccinations have been shifted from the public health service sector to office-based physicians. Today, public health authorities offer mainly supplementary vaccinations. In 2007, protective immunizations were introduced as compulsory benefits of the statutory health insurance (SHI). Recently, the German federal states developed a National Vaccination Plan to support immunization strategies.

Vaccines for the 21st century

PubMed Central

Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

2014-01-01

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

[The variola virus as a biological weapon].

PubMed

Mlinarić-Galinović, Gordana; Turković, Branko; Brudnjak, Zvonimir; Gjenero-Margan, Ira

2003-01-01

In view of the threat of use of the variola virus as a biological weapon, the interest of medical and other public in this causative agent that was eradicated in the wild at the end of the 1970s has increased. The paper gives an outline of the current knowledge on biological properties of the variola virus, and on the epidemiology, pathogenesis, clinical picture and prophylaxis of the disease caused by this virus. Descriptions of two sudden smallpox epidemics (Germany in 1970 and former Yugoslavia in 1972) could illustrate the potential of the smallpox virus as a biological weapon in bioterrorism and biological warfare. In fact, this virus can spread very readily through aerosol, which may lead to explosive epidemics. Not having been immunised, our population aged less than 25 years totally lacks the immunity. Older individuals are likely to have a low residual specific immunity to the agent. The only way to prevent a smallpox epidemic is by vaccination and patient isolation. A rapid smallpox diagnostics and prompt vaccination of all contacts is of utmost importance in stopping the outbreak.

High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

PubMed

Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

2012-11-15

The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

Monkeypox virus and insights into its immunomodulatory proteins

PubMed Central

Weaver, Jessica R.; Isaacs, Stuart N.

2008-01-01

Summary Monkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the US, representing the first documented monkeypox cases in the Western hemisphere. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. There are also differences in genes that code for virulence factors and host range proteins. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances. PMID:18837778

Serological responses in humans to the smallpox vaccine LC16m8

PubMed Central

Johnson, Benjamin F.; Kanatani, Yasuhiro; Fujii, Tatsuya; Saito, Tomoya; Yokote, Hiroyuki

2011-01-01

In response to potential bioterrorism with smallpox, members of the Japanese Self-Defense Forces were vaccinated with vaccinia virus (VACV) strain LC16m8, an attenuated smallpox vaccine derived from VACV strain Lister. The serological response induced by LC16m8 to four virion-surface proteins and the intracellular mature virus (IMV) and extracellular enveloped virus (EEV) was investigated. LC16m8 induced antibody response against the IMV protein A27 and the EEV protein A56. LC16m8 also induced IMV-neutralizing antibodies, but unlike the VACV strain Lister, did not induce either EEV-neutralizing antibody or antibody to EEV protein B5, except after revaccination. Given that B5 is the only target for EEV-neutralizing antibody and that neutralization of both IMV and EEV give optimal protection against orthopoxvirus challenge, these data suggest that immunity induced by LC16m8 might be less potent than that deriving from strain Lister. This potential disadvantage should be balanced against the advantage of the greater safety of LC16m8. PMID:21715598

The Development of Vaccination and the Discoveries of Louis Pasteur.

ERIC Educational Resources Information Center

Williams, James

1992-01-01

Describes the development of vaccination and provides a brief biographical sketch of the life and work of Pasteur. Describes historical practices related to vaccination before Pasteur did his work, including variolation as practiced by the ancient Chinese and Jenner's use of smallpox. (PR)

Interwoven support: an historical survey of US federal programs enabling immunization.

PubMed

Dalrymple, Dack W; Grabenstein, John D

2014-11-28

The US Government (USG) can date its involvement with immunization to military and civilian efforts in 1777 and 1813 to prevent smallpox. USG involvement began accelerating with federal licensing of vaccine and antibody manufacturers in 1903. In addition to ongoing regulation of manufacturing and product quality, military and civilian arms of the USG have led research efforts into new or improved vaccines. These efforts have included diseases endemic in the United States, as well as medical countermeasures targeted against biological weapons, influenza pandemics, and emerging infectious diseases. Especially since the 1950s, the USG has provided increasing levels of funding to purchase vaccines and conduct vaccination programs. These programs have focused largely on children, although vaccination programs for adults have been expanded somewhat in recent years. Multiple agencies of the USG have convened various panels of accomplished external experts who have generated widely regarded recommendations on vaccine safety and efficacy and optimal immunization practices. USG programs for safety assessment, injury compensation, liability protection, and disease surveillance have been developed to assess needs, evaluate safety questions, ensure vaccine supply, and foster confidence in vaccination efforts. Debates on the extent of government involvement date back to the 1890 s and continue today. Several pivotal expansions of government involvement followed disease outbreaks or manufacturing accidents. This historical survey describes each of the major US federal programs in these categories, including references to applicable law. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

PubMed

Mucker, Eric M; Goff, Arthur J; Shamblin, Joshua D; Grosenbach, Douglas W; Damon, Inger K; Mehal, Jason M; Holman, Robert C; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A; Clemmons, Cody J; Hudson, Paul; Hruby, Dennis E

2013-12-01

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans.

Efficacy of Tecovirimat (ST-246) in Nonhuman Primates Infected with Variola Virus (Smallpox)

PubMed Central

Mucker, Eric M.; Goff, Arthur J.; Shamblin, Joshua D.; Grosenbach, Douglas W.; Damon, Inger K.; Mehal, Jason M.; Holman, Robert C.; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A.; Clemmons, Cody J.; Hudson, Paul

2013-01-01

Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917–918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139–13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689–695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768–773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 108 PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo-treated controls that survived infection. Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates, suggesting that it is reasonably likely to provide therapeutic benefit in smallpox-infected humans. PMID:24100494

Can We Capitalize on the Virtues of Vaccines? Insights from the Polio Eradication Initiative

PubMed Central

Aylward, R. Bruce; Heymann, David L.

2005-01-01

Twenty-five years after the eradication of smallpox, the ongoing effort to eradicate poliomyelitis has grown into the largest international health initiative ever undertaken. By 2004, however, the polio eradication effort was threatened by a challenge regularly faced by public health policymakers everywhere—misperception about the benefits and risks of vaccines. The propagation of false rumors about oral poliovirus vaccine safety led to the reinfection of 13 previously polio-free countries and the largest polio epidemic in Africa in recent years. With deft management of such challenges by local, national, and international health authorities, poliomyelitis, a disease that threatened children everywhere just 2 generations ago, could soon be relegated to history like smallpox before it. PMID:15855451

Smallpox DNA Vaccine Protects Nonhuman Primates Against Lethal Monkeypox

DTIC Science & Technology

2004-05-01

skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four...administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting...vaccine to protect rhesus macaques from severe monkeypox. MATERIALS AND METHODS Viruses and cells. The VACV Connaught vaccine strain (derived from the New

17th Century Variola Virus Reveals the Recent History of Smallpox.

PubMed

Duggan, Ana T; Perdomo, Maria F; Piombino-Mascali, Dario; Marciniak, Stephanie; Poinar, Debi; Emery, Matthew V; Buchmann, Jan P; Duchêne, Sebastian; Jankauskas, Rimantas; Humphreys, Margaret; Golding, G Brian; Southon, John; Devault, Alison; Rouillard, Jean-Marie; Sahl, Jason W; Dutour, Olivier; Hedman, Klaus; Sajantila, Antti; Smith, Geoffrey L; Holmes, Edward C; Poinar, Hendrik N

2016-12-19

Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20 th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18 th and 19 th centuries, concomitant with the development of modern vaccination. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

From smallpox eradication to contemporary global health initiatives: enhancing human capacity towards a global public health goal.

PubMed

Tarantola, Daniel; Foster, Stanley O

2011-12-30

The eradication of smallpox owes its success first and foremost to the thousands of lay health workers and community members who, throughout the campaign and across continents, took on the roles of advocates, educators, vaccinators, care providers and contributors to epidemic surveillance and containment. Bangladesh provides a good example where smallpox eradication and the capacity enhancement needed to achieve this goal resulted in a two-way mutually beneficial process. Smallpox-dedicated staff provided community members with information guidance, support and tools. In turn, communities not only created the enabling environment for smallpox program staff to perform their work but acquired the capacity to perform essential eradication tasks. Contemporary global health programmes can learn much from these core lessons including: the pivotal importance of supporting community aspirations, capacity and resilience; the critical need to enhance commitment, capacity and accountability across the workforce; and the high value of attentive human resources management and support. We owe to subsequent global disease control, elimination and eradication ventures recognition of the need for social and behavioural science to inform public health strategies; the essential roles that civil society organizations and public-private partnerships can play in public health discourse and action; the overall necessity of investing in broad-based health system strengthening; and the utility of applying human rights principles, norms and standards to public health policy and practice. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus.

PubMed

Parker, Scott; Crump, Ryan; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Lanier, E Randall; Painter, George; Schriewer, Jill; Trost, Lawrence C; Buller, R Mark

2014-11-01

Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first-generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non-replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered a first response to a smallpox emergency in subjects of uncertain exposure status or as a means of reduction of the incidence and severity of vaccine-associated adverse events. Copyright © 2014 Elsevier B.V. All rights reserved.

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

42 CFR 102.10 - Eligible requesters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION... vaccine recipients, as described in § 102.3(x); (2) Vaccinia contacts, as described in § 102.3(bb); or (3... vaccine recipients or vaccinia contacts (i.e., individuals authorized to act on behalf of the deceased...

The Role of Brincidofovir in Preparation for a Potential Smallpox Outbreak.

PubMed

Foster, Scott A; Parker, Scott; Lanier, Randall

2017-10-30

Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox antivirals with different mechanisms of action available in the event of a smallpox outbreak. Multiple antivirals are recommended due in large part to the propensity of viruses to become resistant to antiviral therapy, especially monotherapy. Advances in synthetic biology heighten concerns that a bioterror attack with variola would utilize engineered resistance to antivirals and potentially vaccines. Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox. Given the devastating potential of smallpox as a bioweapon, preparation of a multi-pronged defense that accounts for the most obvious bioengineering possibilities is strategically imperative.

[A short history of infectious diseases since the fifties of the last century and the importance of vaccination].

PubMed

Marešová, Vilma

2015-01-01

Vaccination in the Czech lands has a long history; it begun during the Austro-Hungarian Empire in 1803 by vaccination against smallpox, and in the late 19th century by vaccination against rabies. In the second half of the 20th century, the basic vaccination included also other vaccines. Thanks to paediatricians, vaccination coverage of children was so high that in addition to the immunity of individuals the collective immunity was also significant. The incidence of infectious diseases has dropped significantly. Today the population, both medical and lay, almost does not know the classic childrens infectious diseases or their risk of complications. This creates a feeling in recent years that vaccination is unnecessary and that it is a source of complication and, therefore, better not to vaccinate. However, diseases, except for smallpox, have not disappeared, and for the susceptible unvaccinated individuals they represent a great risk. There are now occurring at atypical age groups where their diagnosis is even not considered. Therefore, it is important to return to the course of disease as well as to the potentially serious complications in unvaccinated people.

A brief history of vaccines: smallpox to the present.

PubMed

Hsu, Jennifer L

2013-01-01

Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

High-Dimensional Gene Expression Profiling Studies in High and Low Responders to Primary Smallpox Vaccination

PubMed Central

Haralambieva, Iana H.; Oberg, Ann L.; Dhiman, Neelam; Ovsyannikova, Inna G.; Kennedy, Richard B.; Grill, Diane E.; Jacobson, Robert M.; Poland, Gregory A.

2012-01-01

Background. The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. Methods. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. Results. The 20 most significant differentially expressed genes include a tumor necrosis factor–receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E−20, q ≤ 2.64E−17). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E−05). Two pathways (antiviral actions of IFNs, P = 8.95E−05; and IFN-α/β signaling pathway, P = 2.92E−04), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E−05; NR4A2, P ≤ .0002; EGR3, P = 4.52E−05), and other genes with a possible impact on immunity (LNPEP, P = 3.72E−05; CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. Conclusion. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination. PMID:22949304

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

PubMed

Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

2016-01-01

The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.

Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

PubMed

Molina, Chai; Earn, David J D

2015-06-06

Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively). © 2015 The Author(s) Published by the Royal Society. All rights reserved.

The end of the beginning: vaccines for the next 25 years.

PubMed

Oxford, J S

2008-11-18

The first virus vaccines against smallpox and rabies proved their effectiveness even before the ultra microscopic viruses had been identified as a new world of infectious agents. To date most antibacterial and antiviral vaccines have not been designed but rather built step by step. Designer vaccines with T cell epitopes and adjuvants which stimulate innate or acquired immune responses to will are now under serious investigation but have yet to impact on the practical world of infection. The latter is not small, with millions of deaths annually in the world from not uncommon microbes such as enterforms, pneumococci, respiratory and hepatitis viruses and HIV. But can vaccines be used in more social directions to control birth or prevent addiction? Polio should join smallpox this year in the pantheon of eradicated viruses. The infectious disease community can then turn attention to hepatitis B. War has been declared on pandemic influenza but with this zoonotic virus containment is key, with vaccines used alongside antivirals and social distancing. Undoubtedly "we have the guns, and now we can finish the job".

A Comparison of the PRIME-MD PHQ-9 and PHQ-8 in a Large Military Prospective Study, the Millennium Cohort Study

DTIC Science & Technology

2013-03-14

2007. Smallpox vaccination: comparison of self-reported and electronic vaccine records in the Millennium Cohort Study. Human. Vaccine 3, 6. Oquendo...Kim, H.M., McCarthy, J.F., Austin, K.L., Hoggatt, K.J., Walters, H., Valenstein, M., 2007. Suicide mortality among individuals receiving treatment

A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

PubMed

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-04-29

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection

PubMed Central

Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

2010-01-01

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus). A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1–3 days after onset of symptoms, even when very low infectious viral doses of 5×102 pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed. We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID50 (minimal monkey infectious dose 50%) of 8.3×102 pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis. PMID:20454688

Expanding the histological findings in postvaccinial non-viral folliculitis

PubMed Central

Bunick, Christopher G.; Mariwalla, Kavita; Ibrahim, Omer; Modi, Badri; Imaeda, Suguru; McNiff, Jennifer

2014-01-01

Postvaccinial non-viral folliculitis has been recognized in the past decade as a new adverse cutaneous reaction to the smallpox vaccination. Contrary to more serious smallpox vaccine reactions, postvaccinial non-viral folliculitis has a benign course resolving spontaneously within approximately seven days. We describe additional histopathological findings associated with postvaccinial non-viral folliculitis, which has only been described once previously. New findings include the presence of neutrophilic or lymphohistiocytic infiltrates that concentrate around the hair follicles. We compare our findings to the follicular nature of varicella and herpes zoster infections, generating the hypothesis of deposition of vaccinia protein within folliculosebaceous units as a potential pathophysiologic mechanism behind postvaccinial non-viral folliculitis. PMID:23278890

Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.

PubMed

Berhanu, Aklile; Prigge, Jonathan T; Silvera, Peter M; Honeychurch, Kady M; Hruby, Dennis E; Grosenbach, Douglas W

2015-07-01

The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of behavioral changes in a smallpox attack model.

PubMed

Del Valle, S; Hethcote, H; Hyman, J M; Castillo-Chavez, C

2005-06-01

The impact of individual and community behavioral changes in response to an outbreak of a disease with high mortality is often not appreciated. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation of infectives, contact tracing, quarantine of contacts, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. Transmission parameters are estimated from data and an expression is derived for the effective reproduction number. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity rates and to the precautions that the population takes to reduce the transmission of the disease. Even gradual and mild behavioral changes can have a dramatic impact in slowing an epidemic. When behavioral changes are combined with other interventions, the epidemic is shortened and the number of smallpox cases is reduced. We conclude that for simulations of a smallpox outbreak to be useful, they must consider the impact of behavioral changes. This is especially true if the model predictions are being used to guide public health policy.

Live attenuated vaccines: Historical successes and current challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minor, Philip D., E-mail: Philip.Minor@nibsc.org

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up inmore » clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.« less

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon.

PubMed

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K; Alcami, Antonio

2010-05-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.

42 CFR 102.83 - Payment of all benefits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Payment of all benefits. 102.83 Section 102.83 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... vaccine-related injury is hospitalized, but all other documentation is consistent with the requester...

Integrated Analysis of Genetic and Proteomic Data Identifies Biomarkers Associated with Adverse Events Following Smallpox Vaccination

EPA Science Inventory

Complex clinical outcomes, such as adverse reaction to vaccination, arise from the concerted interactions among the myriad components of a biological system. Therefore, comprehensive etiological models can be developed only through the integrated study of multiple types of experi...

Vaccinia Virus Vaccines: Past, Present and Future

PubMed Central

Jacobs, Bertram L.; Langland, Jeffrey O.; Kibler, Karen V.; Denzler, Karen L.; White, Stacy D.; Holechek, Susan A.; Wong, Shukmei; Huynh, Trung; Baskin, Carole R.

2009-01-01

Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third- and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence. PMID:19563829

Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines.

PubMed

Liljeqvist, S; Ståhl, S

1999-07-30

The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case of smallpox, the dream of eradication has been fulfilled. Yet, there is a growing need for improvements of existing vaccines in terms of increased efficacy and improved safety, besides the development of completely new vaccines. Better technological possibilities, combined with increased knowledge in related fields, such as immunology and molecular biology, allow for new vaccination strategies. Besides the classical whole-cell vaccines, consisting of killed or attenuated pathogens, new vaccines based on the subunit principle, have been developed, e.g. the Hepatitis B surface protein vaccine and the Haemophilus influenzae type b vaccine. Recombinant techniques are now dominating in the strive for an ideal vaccine, being safe and cheap, heat-stable and easy to administer, preferably single-dose, and capable of inducing broad immune response with life-long memory both in adults and in infants. This review will describe different recombinant approaches used in the development of novel subunit vaccines, including design and production of protein immunogens, the development of live delivery systems and the state-of-the-art for nucleic acids vaccines.

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

DOE PAGES

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; ...

2015-03-20

Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.« less

A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination

PubMed Central

Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.

2015-01-01

Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized. PMID:25793705

A Study of Waste Management within the COL Florence A. Blanchfield Army Community Hospital, Fort Campbell, Kentucky.

DTIC Science & Technology

1981-08-01

besnoiti Borna disease virus Bovine infectious petechial fever virus Camel pox virus Ephemeral fever virus Fowl plague virus Goat pox virus Hog...Varicella virus Vole rickettsia Yellow fever virus, 17D vaccine strain 69 Class 3 Alastrun, smallpox, monkeypox, and whitepox, when used in vitro Arbovirus...animal inoculation experiments Vesicular stomatitis virus Yellow fever virus - wild when used in vitro Class 4 Alastrun, smallpox, monkeypox, and

Childhood vaccination: achievements and challenges.

PubMed

Ndumbe, P

1996-09-01

As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

Preinjury Psychological Status, Injury Severity and Postdeployment Posttraumatic Stress Disorder

DTIC Science & Technology

2011-05-01

Millennium Cohort Study Team. Smallpox vaccination : comparison of self-reported and electronic vaccine records in the Millennium Cohort Study. Hum Vaccin ...Smith B, Leard CA, Smith TC, Reed RJ, Ryan MAK; Millennium Cohort Study Team. Anthrax vaccination in the Millennium Cohort: validation and measures of...in Adults With Autism Spectrum Dis- orders” by Suzuki et al, published in the March 2011 is- sue of the Archives (2011;68(3):306-313), some figure

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) vaccine in recipients (R); or (2) exposure to vaccinia in contacts (C). Please note that these time... contact requires sufficient evidence in the medical records of the occurrence of a significant local skin... recipient or contact requires sufficient evidence in the medical records of the occurrence of SJS. The SJS...

Particulate delivery systems for biodefense subunit vaccines.

PubMed

Bramwell, Vincent W; Eyles, Jim E; Oya Alpar, H

2005-06-17

Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

Medical experimentation concerning chemical and biological weapons for mass destruction.

PubMed

Deutsch, Erwin

2003-04-01

This article is the text of a speech originally presented at the Second World Conference on Medical Ethics at Gijon, Spain, on 2 October 2002 under the title "Medical Experimentation Concerning Chemical and Biological Weapons for Mass Destruction: Clinical Design for New Smallpox Vaccines: Ethical and Legal Aspects." Experimentation on vaccines such as smallpox is subject to the usual ethical rules such as the need for informed consent. However, the participants will not often be at risk of catching the disease but expose themselves by taking part in the experimentation. Professor Deutsch explores the implications of this, including the position of vulnerable groups such as children, those with mental handicaps, and those acting under orders such as the miliary, the policy and fire officers.

The generation of CD8+ T-cell population specific for vaccinia virus epitope involved in the antiviral protection against ectromelia virus challenge.

PubMed

Gierynska, Malgorzata; Szulc-Dabrowska, Lidia; Dzieciatkowski, Tomasz; Golke, Anna; Schollenberger, Ada

2015-12-01

Eradication of smallpox has led to cessation of vaccination programs. This has rendered the human population increasingly susceptible not only to variola virus infection but also to infections with other representatives of Poxviridae family that cause zoonotic variola-like diseases. Thus, new approaches for designing improved vaccine against smallpox are required. Discovering that orthopoxviruses, e.g. variola virus, vaccinia virus, ectromelia virus, share common immunodominant antigen, may result in the development of such a vaccine. In our study, the generation of antigen-specific CD8(+) T cells in mice during the acute and memory phase of the immune response was induced using the vaccinia virus immunodominant TSYKFESV epitope and CpG oligodeoxynucleotides as adjuvants. The role of the generated TSYKFESV-specific CD8(+) T cells was evaluated in mice during ectromelia virus infection using systemic and mucosal model. Moreover, the involvement of dendritic cells subsets in the adaptive immune response stimulation was assessed. Our results indicate that the TSYKFESV epitope/TLR9 agonist approach, delivered systemically or mucosally, generated strong CD8(+) T-cell response when measured 10 days after immunization. Furthermore, the TSYKFESV-specific cell population remained functionally active 2 months post-immunization, and gave cross-protection in virally challenged mice, even though the numbers of detectable antigen-specific T cells decreased. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ethical and legal challenges of vaccines and vaccination: Reflections.

PubMed

Jesani, Amar; Johari, Veena

2017-01-01

Vaccines and vaccination have emerged as key medical scientific tools for prevention of certain diseases. Documentation of the history of vaccination shows that the initial popular resistance to universal vaccination was based on false assumptions and eventually gave way to acceptance of vaccines and trust in their ability to save lives. The successes of the global eradication of smallpox, and now of polio, have only strengthened the premier position occupied by vaccines in disease prevention. However, the success of vaccines and public trust in their ability to eradicate disease are now under challenge, as increasing numbers of people refuse vaccination, questioning the effectiveness of vaccines and the need to vaccinate.

Overproduction, purification, and biochemical characterization of the dual specificity H1 protein phosphatase encoded by variola major virus.

PubMed

Tropea, Joseph E; Phan, Jason; Waugh, David S

2006-11-01

Smallpox, a highly contagious infectious disease caused by the variola major virus, has an overall mortality rate of about 30%. Because there currently is no specific treatment for smallpox, and the only prevention is vaccination, there is an urgent need for the development of effective antiviral drugs. The dual specificity protein phosphatase encoded by the smallpox virus (H1) is essential for the production of infectious viral particles, making it a promising molecular target for antiviral therapeutics. Here, we report the molecular cloning, overproduction, purification, and initial biochemical characterization of H1 phosphatase, thereby paving the way for the discovery of small molecule inhibitors.

[Smallpox preparedness in Denmark].

PubMed

Heegaard, Erik Deichmann; Fomsgaard, Anders

2005-09-05

Although the likelihood of a deliberate release is considered to be minor, smallpox virus poses a worldwide terrorism security risk because it (1) can easily be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential to create a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. Consequently, Statens Serum Institute and the National Board of Health have developed a Danish smallpox preparedness plan. This article discusses critical aspects of the plan, including risk analysis and a multi-tiered action plan, vaccination, analysis of clinical specimens, the establishment of active surveillance teams and generic contingency elements.

Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology.

PubMed

Rodrigues, Ana F; Soares, Hugo R; Guerreiro, Miguel R; Alves, Paula M; Coroadinha, Ana S

2015-09-01

Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus-like particles, vectored vaccines and chimeric vaccines requires the use - and often the development - of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Jennerian vaccination and the creation of a national public health agenda in Japan, 1850-1900.

PubMed

Jannetta, Ann

2009-01-01

Vaccination played a leading role in transforming the social and political status of medicine in Japanese society in the second half of the nineteenth century. The process began well before the Meiji Restoration of 1868 created a centralized government under the Japanese emperor. At the beginning of the century, medicine was a private business. There was no oversight from an interested government, and there were no medical societies or journals in which to debate and formulate opinion about medical practice. Medical knowledge was transmitted privately through personal lineage structures whose members jealously guarded their medical techniques. For almost a half century before live vaccine could be imported, knowledge of vaccination was limited to a small group of Japanese physicians who could read Dutch. This special knowledge created a medical elite whose members managed the transmission of vaccination after the vaccine arrived, and dominated the new medical and public health bureaucracies created by the Meiji state. By the end of the century, a rigorous vaccination program was in place, smallpox mortality had fallen, and Japan's Western-oriented physicians were in control of a national public health bureaucracy that could monitor the vaccination status of individuals in households throughout Japan.

The Role of Research in Viral Disease Eradication and Elimination Programs: Lessons for Malaria Eradication

PubMed Central

Breman, Joel G.; de Quadros, Ciro A.; Dowdle, Walter R.; Foege, William H.; Henderson, Donald A.; John, T. Jacob; Levine, Myron M.

2011-01-01

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases—smallpox, poliomyelitis, and measles—we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios. PMID:21311582

Adolescent Immunization: Challenges and Opportunities

ERIC Educational Resources Information Center

Grace, Judith A.

2006-01-01

Immunization is one of the greatest public health achievements of the past century. Vaccines are responsible for the worldwide eradication of smallpox, the elimination of polio in the western hemisphere, and most recently the elimination of rubella as a public health threat in the United States. Childhood vaccination rates are at an all-time high,…

[Smallpox is a dormant volcano].

PubMed

L'vov, D K; Zverev, V V; Gintsburg, A L; Marennikova, S S; Pal'tsev, M A

2008-01-01

The presence of rodent-associated natural foci containing at least 6 of the known 11 viruses belonging to the genus Orthopoxvirus (Poxviridae, Chordopoxvirinae) within the equatorial, tropical, subtropical, temperate, and subarctic climatic zones; the increasing aggravation of the monkey pox epidemic situation in equatorial Africa with an increase in human mortality by an average of 9.8% with a possibility of 2 to 8 passages in 30-70% of patients; the possible persistence of a virus in the human cadavers buried in the permafrost of Eurasia and America; bioterrorism threat due to the unaccounted viral reserves persisting somewhere or somebody; no postvaccinal human immunity since vaccination and vaccine manufacture stopped 30 years ago as recommended by the WHO, make the risk of the deteriorating epidemic situation with disastrous effects greater now and in the foreseeable future than it was 20-30 years ago. Health care academic circles and bodies do not know methods for rapid diagnosis in the field conditions of species-specific identification smallpox virus or preventive (low-reactogenic, effective vaccines, and those accessible for mass production) and therapeutic (nontoxic drugs, those satisfactory for mass production, inexpedient, effective ones when orally used) agents. Basic studies of biodiversity, functional properties of viral DNA and proteins, pathogenesis, and evolution are required. Live smallpox virus should be used at certain and particularly final stages for these studies that are of scientific and applied significance.

Women and vaccinations: From smallpox to the future, a tribute to a partnership benefiting humanity for over 200 years.

PubMed

Datta, Sanjoy Kumar; Bhatla, Neerja; Burgess, Margaret A; Lehtinen, Matti; Bock, Hans Ludwig

2009-07-01

Vaccines were first developed in England over 200 years ago and have made a significant positive impact on human society since. Not often realized is the intimate relationship shared between vaccines and women. Women were key to the initial development of vaccines; some were even advocating the concept of protection against infectious disease through prior asymptomatic infection (by variolation) before the publication of the report of the first successful smallpox vaccination in 1798. Since that milestone, women have been important partners in the development of vaccines and advocates for their widespread introduction. Modern vaccine development would not be possible without the altruistic informed consent granted by many women for the participation of themselves or their children in vaccine clinical trials all over the world. Vaccines have rewarded women handsomely in return. Individual women benefit in many ways ranging from safer pregnancies to preventing cancers to attractive, unblemished skin. Some vaccines are even specifically designed to prevent diseases primarily affecting women such as cervical cancer. Vaccines also have offered societal benefits to women. These include better maternal health and fostering an environment more amenable to effective family planning. With these advances, women become more empowered and have access to better economic opportunities. The challenge of meeting the millennium development goals specifically targeted for women will be facilitated by vaccines. A better realization by women of the benefits of this partnership secured over the past 200 years will enable them to reap fully the rewards of the future.

Vaccination with a codon-optimized A27L-containing plasmid decreases virus replication and dissemination after vaccinia virus challenge.

PubMed

Martínez, Osmarie; Bravo Cruz, Ariana; Santos, Saritza; Ramírez, Maite; Miranda, Eric; Shisler, Joanna; Otero, Miguel

2017-10-20

Smallpox is a disease caused by Variola virus (VARV). Although eradicated by WHO in 1980, the threat of using VARV on a bioterror attack has increased. The current smallpox vaccine ACAM2000, which consists of live vaccinia virus (VACV), causes complications in individuals with a compromised immune system or with previously reported skin diseases. Thus, a safer and efficacious vaccine needs to be developed. Previously, we reported that our virus-free DNA vaccine formulation, a pVAX1 plasmid encoding codon-optimized VACV A27L gene (pA27LOPT) with and without Imiquimod adjuvant, stimulates A27L-specific production of IFN-γ and increases humoral immunity 7days post-vaccination. Here, we investigated the immune response of our novel vaccine by measuring the frequency of splenocytes producing IFN-γ by ELISPOT, the TH1 and TH2 cytokine profiles, and humoral immune responses two weeks post-vaccination, when animals were challenged with VACV. In all assays, the A27-based DNA vaccine conferred protective immune responses. Specifically, two weeks after vaccination, mice were challenged intranasally with vaccinia virus, and viral titers in mouse lungs and ovaries were significantly lower in groups immunized with pA27LOPT and pA27LOPT+Imiquimod. These results demonstrate that our vaccine formulation decreases viral replication and dissemination in a virus-free DNA vaccine platform, and provides an alternative towards a safer an efficacious vaccine. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Eighteen-ninety-six and all that

NASA Astrophysics Data System (ADS)

Heilbron, J. L.

1996-01-01

This year's commemorative platter includes ether anaesthesia, smallpox vaccination, radioactivity and several mathematical morsels, as well as an accidental death (Otto Lilienthal) and the mother of all births (the Universe).

[Smallpox in Ferrara in the nineteenth century].

PubMed

Guidi, Enrica; Angelini, Lauretta; Cervato, Katia; Pizzo, Francesco; Rizzetto, Roberto; Fortini, Marco; Contini, Carlo

2007-03-01

The aim of this work was to analyse the mortality for smallpox and the methods used during the nineteenth-century to control epidemics. Most of the historical material was found in the Historical Archives of the Ferrara City Council. Over the whole period in question, there were 710 deaths in Ferrara (366 males and 344 females). The highest number was found in the years 1816, 1829, 1834, 1842, 1849, 1871 and 1891. Data analysis shows that most deaths occurred during the first half of the century. Subsequently, the phenomenon declined to almost zero. Males were more affected and nearly 70% of the deaths occurred under 5 years of age, 50%of which during the first year of life. At that time, the "guidelines" adopted were analogous to those currently followed when a new vaccination programme is started. The inspiring principles were the active and free supply of vaccine, universal vaccination, the informed consent of the population, the involvement of educators and also monetary rewards to the most industrious doctors in the practice of vaccination. In Ferrara vaccination began in 1801, but was only consistently implemented in 1812. By the end of the 19th century the number of persons vaccinated had increased from 3% to 7%. Vaccination initiatives assumed great importance among the population of Ferrara, in spite of initial resistance and suspicion of a practice which most people found incomprehensible.

Smallpox subunit vaccine produced in planta confers protection in mice

PubMed Central

Golovkin, Maxim; Spitsin, Sergei; Andrianov, Vyacheslav; Smirnov, Yuriy; Xiao, Yuhong; Pogrebnyak, Natalia; Markley, Karen; Brodzik, Robert; Gleba, Yuri; Isaacs, Stuart N.; Koprowski, Hilary

2007-01-01

We report here the in planta production of the recombinant vaccinia virus B5 antigenic domain (pB5), an attractive component of a subunit vaccine against smallpox. The antigenic domain was expressed by using efficient transient and constitutive plant expression systems and tested by various immunization routes in two animal models. Whereas oral administration in mice or the minipig with collard-derived insoluble pB5 did not generate an anti-B5 immune response, intranasal administration of soluble pB5 led to a rise of B5-specific immunoglobulins, and parenteral immunization led to a strong anti-B5 immune response in both mice and the minipig. Mice immunized i.m. with pB5 generated an antibody response that reduced virus spread in vitro and conferred protection from challenge with a lethal dose of vaccinia virus. These results indicate the feasibility of producing safe and inexpensive subunit vaccines by using plant production systems. PMID:17428917

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

E3L and F1L Gene Functions Modulate the Protective Capacity of Modified Vaccinia Virus Ankara Immunization in Murine Model of Human Smallpox.

PubMed

Volz, Asisa; Jany, Sylvia; Freudenstein, Astrid; Lantermann, Markus; Ludwig, Holger; Sutter, Gerd

2018-01-04

The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L . Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice. In non-permissive human tissue culture the MVA deletion mutant viruses produced reduced levels of the VACV envelope antigen B5. Upon mousepox challenge at three weeks after vaccination, MVA-ΔF1L and MVA-ΔE3L exhibited reduced protective capacity in comparison to wildtype MVA. Surprisingly, however, all vaccines proved equally protective against a lethal ECTV infection at two days after vaccination. Accordingly, the deletion mutant MVA vaccines induced high levels of virus-specific CD8+ T cells previously shown to be essential for rapidly protective MVA vaccination. These results suggest that inactivation of the anti-apoptotic genes F1L or E3L modulates the protective capacity of MVA vaccination most likely through the induction of distinct orthopoxvirus specific immunity in the absence of these viral regulatory proteins.

Genomic Sequence and Virulence of Clonal Isolates of Vaccinia Virus Tiantan, the Chinese Smallpox Vaccine Strain

PubMed Central

Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

2013-01-01

Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector. PMID:23593246

Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

PubMed

Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

2013-01-01

Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

Logistics in smallpox: the legacy.

PubMed

Wickett, John; Carrasco, Peter

2011-12-30

Logistics, defined as "the time-related positioning of resources" was critical to the implementation of the smallpox eradication strategy of surveillance and containment. Logistical challenges in the smallpox programme included vaccine delivery, supplies, staffing, vehicle maintenance, and financing. Ensuring mobility was essential as health workers had to travel to outbreaks to contain them. Three examples illustrate a range of logistic challenges which required imagination and innovation. Standard price lists were developed to expedite vehicle maintenance and repair in Bihar, India. Innovative staffing ensured an adequate infrastructure for vehicle maintenance in Bangladesh. The use of disaster relief mechanisms in Somalia provided airlifts, vehicles and funding within 27 days of their initiation. In contrast the Expanded Programme on Immunization (EPI) faces more complex logistical challenges. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

PubMed Central

Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

2012-01-01

Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’

PubMed Central

Weiss, Robin A.; Esparza, José

2015-01-01

Sir Hans Sloane's account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family's children. When Edward Jenner's inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750241

Genetic resistance to smallpox: lessons from mousepox.

PubMed

Karupiah, Gunasegaran; Panchanathan, Vijay; Sakala, Isaac G; Chaudhri, Geeta

2007-01-01

There is increased interest in understanding protective immunity to smallpox for two principal reasons. First, it is the only disease that has been successfully eradicated using a live virus vaccine and, second, there exists a potential threat of intentional or unintentional release of variola virus, the causative agent of smallpox. Although mortality rates associated with smallpox were as high as 40%, a significant subset of those infected recovered. The basis of susceptibility or resistance, and the immune parameters associated with recovery, are still unknown. Animal models of poxvirus infections are being employed to understand what constitutes an effective host response. Ectromelia virus is closely related to variola virus and it causes a disease similar to smallpox in mice. This model is well established, resistant and susceptible strains of mice are defined and four genetic loci associated with resistance have been identified. Susceptibility to infec tion and disease severity is also influenced by virus immune evasion strategies. The outcome of infection is clearly dictated by several factors including host and viral genes, both of which influence the immune response. Here we present data on one virus-encoded immune modifier and its effect on the functions of two host genetic loci associ ated with resistance.

Therapeutic options for diseases due to potential viral agents of bioterrorism.

PubMed

Bronze, Michael S; Greenfield, Ronald A

2003-02-01

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon

PubMed Central

Fernández de Marco, María del Mar; Alejo, Alí; Hudson, Paul; Damon, Inger K.; Alcami, Antonio

2010-01-01

Variola virus (VARV) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. Virulent orthopoxviruses infecting humans, such as monkeypox virus (MPXV), could fill the niche left by smallpox eradication and the cessation of vaccination. However, immunomodulatory activities and virulence determinants of VARV and MPXV remain largely unexplored. We report the molecular characterization of the VARV- and MPXV-secreted type I interferon-binding proteins, which interact with the cell surface after secretion and prevent type I interferon responses. The proteins expressed in the baculovirus system have been purified, and their interferon-binding properties characterized by surface plasmon resonance. The ability of these proteins to inhibit a broad range of interferons was investigated to identify potential adaptation to the human immune system. Furthermore, we demonstrate by Western blot and activity assays the expression of the type I interferon inhibitor during VARV and MPXV infections. These findings are relevant for the design of new vaccines and therapeutics to smallpox and emergent virulent orthopoxviruses because the type I interferon-binding protein is a major virulence factor in animal models, vaccination with this protein induces protective immunity, and its neutralization prevents disease progression.—Fernández de Marco, M. M., Alejo, A., Hudson, P., Damon, I. K., Alcami, A. The highly virulent variola and monkeypox viruses express secreted inhibitors of type I interferon. PMID:20019241

Contingency planning for a deliberate release of smallpox in Great Britain--the role of geographical scale and contact structure.

PubMed

House, Thomas; Hall, Ian; Danon, Leon; Keeling, Matt J

2010-02-14

In the event of a release of a pathogen such as smallpox, which is human-to-human transmissible and has high associated mortality, a key question is how best to deploy containment and control strategies. Given the general uncertainty surrounding this issue, mathematical modelling has played an important role in informing the likely optimal response, in particular defining the conditions under which mass-vaccination would be appropriate. In this paper, we consider two key questions currently unanswered in the literature: firstly, what is the optimal spatial scale for intervention; and secondly, how sensitive are results to the modelling assumptions made about the pattern of human contacts? Here we develop a novel mathematical model for smallpox that incorporates both information on individual contact structure (which is important if the effects of contact tracing are to be captured accurately) and large-scale patterns of movement across a range of spatial scales in Great Britain. Analysis of this model confirms previous work suggesting that a locally targeted 'ring' vaccination strategy is optimal, and that this conclusion is actually quite robust for different socio-demographic and epidemiological assumptions. Our method allows for intuitive understanding of the reasons why national mass vaccination is typically predicted to be suboptimal. As such, we present a general framework for fast calculation of expected outcomes during the attempted control of diverse emerging infections; this is particularly important given that parameters would need to be interactively estimated and modelled in any release scenario.

Comparison of Clinical Presentation of Acute Myocarditis Following Smallpox Vaccination to Acute Coronary Syndromes in Patients 40 Years of Age

DTIC Science & Technology

2005-05-15

539–543. 4. Kuhl U, Pauschinger M, Bock T, Klingel K, Schwimmbeck CP, Seeberg B, Krautwurm L, Poller W, Schultheiss HP, Kandolf R. Parvovirus B19 ... parvoviruses and have been unrelated to vaccinations.2–4 It is unknown whether the presentations of those patients would be substantially different from

Unusual Features of Vaccinia Virus Extracellular Virion Form Neutralization Resistance Revealed in Human Antibody Responses to the Smallpox Vaccine

PubMed Central

Benhnia, Mohammed Rafii-El-Idrissi; Maybeno, Matthew; Blum, David; Aguilar-Sino, Rowena; Matho, Michael; Meng, Xiangzhi; Head, Steven; Felgner, Philip L.; Zajonc, Dirk M.; Koriazova, Lilia; Kato, Shinichiro; Burton, Dennis R.; Xiang, Yan; Crowe, James E.; Peters, Bjoern

2013-01-01

The extracellular virion form (EV) of vaccinia virus (VACV) is essential for viral pathogenesis and is difficult to neutralize with antibodies. Why this is the case and how the smallpox vaccine overcomes this challenge remain incompletely understood. We previously showed that high concentrations of anti-B5 antibodies are insufficient to directly neutralize EV (M. R. Benhnia, et al., J. Virol. 83:1201–1215, 2009). This allowed for at least two possible interpretations: covering the EV surface is insufficient for neutralization, or there are insufficient copies of B5 to allow anti-B5 IgG to cover the whole surface of EV and another viral receptor protein remains active. We endeavored to test these possibilities, focusing on the antibody responses elicited by immunization against smallpox. We tested whether human monoclonal antibodies (MAbs) against the three major EV antigens, B5, A33, and A56, could individually or together neutralize EV. While anti-B5 or anti-A33 (but not anti-A56) MAbs of appropriate isotypes were capable of neutralizing EV in the presence of complement, a mixture of anti-B5, anti-A33, and anti-A56 MAbs was incapable of directly neutralizing EV, even at high concentrations. This remained true when neutralizing the IHD-J strain, which lacks a functional version of the fourth and final known EV surface protein, A34. These immunological data are consistent with the possibility that viral proteins may not be the active component of the EV surface for target cell binding and infectivity. We conclude that the protection afforded by the smallpox vaccine anti-EV response is predominantly mediated not by direct neutralization but by isotype-dependent effector functions, such as complement recruitment for antibodies targeting B5 and A33. PMID:23152530

Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

PubMed

Volz, A; Sutter, G

2017-01-01

Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

Personalized vaccines: the emerging field of vaccinomics

PubMed Central

Poland, Gregory A; Ovsyannikova, Inna G; Jacobson, Robert M

2010-01-01

The next ‘golden age’ in vaccinology will be ushered in by the new science of vaccinomics. In turn, this will inform and allow the development of personalized vaccines, based on our increasing understanding of immune response phenotype: genotype information. Rapid advances in developing such data are already occurring for hepatitis B, influenza, measles, mumps, rubella, anthrax and smallpox vaccines. In addition, newly available data suggest that some vaccine-related adverse events may also be genetically determined and, therefore, predictable. This paper reviews the basis and logic of personalized vaccines, and describes recent advances in the field. PMID:18847302

Social contact networks and disease eradicability under voluntary vaccination.

PubMed

Perisic, Ana; Bauch, Chris T

2009-02-01

Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in populations where voluntary vaccination is the primary control mechanism may depend partly on whether the disease is transmissible only to a few close social contacts or to a larger subset of the population.

Smallpox: can we still learn from the journey to eradication?

PubMed

Smith, Kendall A

2013-05-01

One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

Adverse events post smallpox-vaccination: insights from tail scarification infection in mice with Vaccinia virus.

PubMed

Mota, Bruno E F; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A; Vieira, Leda Q; da Fonseca, Flávio G; Ferreira, Paulo C P; Bonjardim, Cláudio A; Damon, Inger K; Kroon, Erna G

2011-04-15

Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1(-/-)) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1(-/-) with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1(-/-), and passive transfer of WT T cells to Rag1(-/-) animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify individuals with higher risk of complications after infection with poxvirus.

Tdap Booster Requirements for Secondary Schools

MedlinePlus

... HPV Rubella Influenza Smallpox Measles Tetanus MenACWY Varicella (chickenpox) MenB Zoster (shingles) Mumps View All Pertussis Talking ... TRANSLATE FOR IAC TRAVEL (INTERNATIONAL) UNPROTECTED PEOPLE REPORTS Chickenpox Diphtheria Hepatitis A Hepatitis B >> view all VACCINATING ...

What Would Happen If We Stopped Vaccinations?

MedlinePlus

... of the last century, diseases like whooping cough, polio, measles, Haemophilus influenzae , and rubella struck hundreds of ... smallpox — has been totally erased from the planet. Polio is close to being eliminated, but still exists ...

BERNA: a century of immunobiological innovation.

PubMed

Cryz, S J

1999-10-01

At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic, when administered by the intranasal route.

The history of vaccines and immunization: familiar patterns, new challenges.

PubMed

Stern, Alexandra Minna; Markel, Howard

2005-01-01

Human beings have benefited from vaccines for more than two centuries. Yet the pathway to effective vaccines has been neither neat nor direct. This paper explores the history of vaccines and immunization, beginning with Edward Jenner's creation of the world's first vaccine for smallpox in the 1790s. We then demonstrate that many of the issues salient in Jenner's era-such as the need for secure funding mechanisms, streamlined manufacturing and safety concerns, and deep-seated public fears of inoculating agents-have frequently reappeared and have often dominated vaccine policies. We suggest that historical awareness can help inform viable long-term solutions to contemporary problems with vaccine research, production, and supply.

Smallpox DNA Vaccine Delivered by Novel Skin Electroporation Device Protects Mice Against Intranasal Poxvirus Challenge

DTIC Science & Technology

2006-11-27

response being elicited by microneedle -mediated skin electroporation. 2006 Elsevier Ltd. All rights reserved. i o a p ( c o t t v H f r eywords...localized skin infection containing infectious virus (i.e., ock), the infection can spread to other sites on the body e.g., ocular autoinoculation) or to...plasmid DNA-coated microneedle arrays. Mice vaccinated with the 4pox DNA vaccine mounted robust antibody responses against the four immunogens-of-interest

Historical aspects of immunization and vaccine safety communication.

PubMed

Helfert, Stephanie M

2015-01-01

It has been a long journey starting from the beginnings of variolation [3] leading up to the greatest success in the history of immunization: the eradication of smallpox [39]. Today, vaccines are an acknowledged important medical advance [40]. Nevertheless, immunization has been the subject of public controversy on several occasions [15, 24, 31]. This article shall provide a short overview of some aspects of the early stages of immunization in Western countries, including some examples of vaccine safety controversies in the past.

[Old and new prescriptions for infectious diseases and the newest recipes for biomedical products in plants].

PubMed

Koprowski, Hilary

2002-01-01

The three antiviral vaccines discovered in the 18th century (smallpox), 19th century (rabies), and 20th century (polio) share a common feature: none would ever be licensed today for human vaccination. Yet Jenner's smallpox vaccine led to the eradication of smallpox, Pasteur's rabies vaccine represented the first successful post-exposure treatment of people bitten by rabid animals, and polio vaccine administered since its discovery in 1950 is leading to the eradication of polio (in the years 2004-2005) from the earth. However, in the case of rabies, efforts at complete eradication are unrealistic, despite the availability of a very effective vaccine, since rabies, unlike smallpox and polio, is not limited to humans and can infect all domestic and wild mammalian species. Rabies is probably the oldest known infectious disease, yet knowledge of the virus and the disease is far from complete. For instance, the appearance of 24 cases of "cryptic" rabies in the USA, i.e. cases not associated with any bite or scratch, with an incubation period in humans extending 6-8 years, is a puzzling phenomenon that cannot be readily explained. On the other hand, rabies is one of the few strictly neuronal infections and, as such, is an excellent model for the study of neurotropic virus distribution in the brain. Apoptosis induced by a rabies strain expressing high levels of glycoprotein spreads much more slowly through brain tissue than that induced by strains producing lower glycoprotein levels. Attenuated rabies virus constructed to express twice the normal glycoprotein levels is also an excellent antigen for induction of immune responses in the host. Foreign antigens using this vector may also produce highly immunogenic vaccines. Global approach to immunization. Those monitoring the spread of AIDS in many parts of the world know that cost of treatment is one of the major problems in combating the disease. Vaccines against HIV face the same problem. In general, the price of vaccines and sera is exorbitant for the afflicted population in developing countries. In addition, the dearth of syringes, the unavailability of nurses and doctors to administer multiple vaccine injections, and other factors in these countries require a drastic change in current vaccine production approaches. About 12 years ago, plants became vehicles to produce biomedical reagents. Plants can be exposed directly to a construct containing a foreign gene and Agrobacterium to create a transgenic plant that, over several generations, produces the desired product. Alternatively, plants infected with a plant virus (e.g. alfalfa mosaic virus) fused with a foreign gene can propagate the foreign antigen as the virus multiplies. Extraction of the plant virus followed by purification provides the desired biomedical product. Our use of either of these systems has led to the creation of plants producing vaccines, sera, hormones, and other biological reagents. In two clinical trials at the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań (Poland), volunteers who ingested lettuce expressing hepatitis B vaccine showed hepatitis B antibodies in their sera. In another trial carried out at the Biotechnology Foundation Laboratories in Philadelphia (USA), volunteers ingesting a spinach-rabies vaccine showed an immunological priming effect, since only one injection of commercially available rabies vaccine significantly raised the level of rabies-specific antibodies. Vaccines against HIV gp120 and Tat have been produced in spinach, and a construct of gp120 with the CD4 receptor is now being adapted to this plant. Two types of antibodies against rabies and against colorectal cancer are being produced in tobacco and in lettuce. The suboptimal quality of the currently available anthrax vaccine prompted our efforts to produce the anthrax protective antigen (PA) in tobacco and lettuce. Quite clearly, plants will play a prominent role in producing a variety of biomedical reagents in the future.

[International health regulations--evaluation and trends].

PubMed

Vessereau, A

1988-01-01

The current International Health Regulations (IHR) were adopted by the Twenty-second World Health Assembly in 1969 and amended in 1973 and 1981. They are a revised and consolidated version of the International Sanitary Regulations which were adopted by the Fourth World Health Assembly in 1951, themselves based on the previous International Sanitary Conventions. The purpose of the IHR is to ensure maximum security against the international spread of diseases with a minimum interference to world traffic. Over the years the IHR included cholera, yellow fever, plague, smallpox, typhus and relapsing fever, and then dropped the last three as a result of the global eradication of smallpox and the decline of typhus and relapsing fever as international threats. The IHR have played and still play an important part with respect to the diseases for which they were drawn up. The international spread of yellow fever has been contained by the application of a highly effective vaccine to travellers, and of plague by the inspection of ships and aircrafts for rats, and improvements in the design of air and sea cargo carriers to make them increasingly uninhabitable for rats. The role of the IHR was questioned as far as smallpox and cholera are concerned by arguing that smallpox was eradicated by rigorous national local vaccination programmes and cholera must be defeated by improved environmental sanitation. However, one must not lose sight of the fact that an important element of the IHR is the obligation to notify cases of the diseases listed, together with as much epidemiological information as possible, in order to permit other countries to take appropriate action.(ABSTRACT TRUNCATED AT 250 WORDS)

Genome-Wide Analysis of Polymorphisms Associated with Cytokine Responses in Smallpox Vaccine Recipients

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Pankratz, V. Shane; Haralambieva, Iana H.; Vierkant, Robert A.; Poland, Gregory A.

2014-01-01

The role that genetics plays in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host-pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in smallpox vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences vaccine responses. PMID:22610502

Military Health: DOD’s Vaccine Healthcare Centers Network

DTIC Science & Technology

2007-06-29

example, according to CDC’s Morbidity and Mortality Weekly Report of May 18, 2007, a child of a servicemember who received the smallpox vaccine...must be rated as “fully medically ready.” To meet this requirement, among other things, servicemembers must receive all immunizations that, depending...Diphtheria, hepatitis A, hepatitis B, influenza, measles , meningococcal disease, mumps, pertussis, poliovirus, rubella, tetanus, varicella, yellow

History of Smallpox and Its Spread in Human Populations.

PubMed

Thèves, Catherine; Crubézy, Eric; Biagini, Philippe

2016-08-01

Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.

76 FR 49776 - The Development and Evaluation of Next-Generation Smallpox Vaccines; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

... antibodies and cell- mediated immune responses, with both clinical and immunological outcomes similar to... appropriate, and to comparative human immune response data. As for any biologic product, licensure of new...

A randomized, double-blind, controlled clinical trial to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy volunteers.

PubMed

Jang, Hee-Chang; Kim, Choong Jong; Kim, Kye Hyoung; Lee, Kwang-Hee; Byun, Young-Ho; Seong, Baik-Lin; Saletti, Giulietta; Czerkinsky, Cecil; Park, Wan Beom; Park, Sang-Won; Kim, Hong-Bin; Kim, Nam Joong; Oh, Myoung-don

2010-08-16

A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 99.2% (122/123), and 90.8% (109/120), respectively, and these rates did not differ significantly between the conventional-dose and the low-dose CJ-50300 (1.0x10(8) and 1.0x10(7) plaque-forming units/mL, respectively) (P>0.05 for each). No serious adverse reaction was observed. However, one case of possible generalized vaccinia occurred in the conventionally dosed group [ClinicalTrials.gov Identifier: NCT00607243].

Hybrid grammar-based approach to nonlinear dynamical system identification from biological time series

NASA Astrophysics Data System (ADS)

McKinney, B. A.; Crowe, J. E., Jr.; Voss, H. U.; Crooke, P. S.; Barney, N.; Moore, J. H.

2006-02-01

We introduce a grammar-based hybrid approach to reverse engineering nonlinear ordinary differential equation models from observed time series. This hybrid approach combines a genetic algorithm to search the space of model architectures with a Kalman filter to estimate the model parameters. Domain-specific knowledge is used in a context-free grammar to restrict the search space for the functional form of the target model. We find that the hybrid approach outperforms a pure evolutionary algorithm method, and we observe features in the evolution of the dynamical models that correspond with the emergence of favorable model components. We apply the hybrid method to both artificially generated time series and experimentally observed protein levels from subjects who received the smallpox vaccine. From the observed data, we infer a cytokine protein interaction network for an individual’s response to the smallpox vaccine.

Vaccinia Virus Induces Rapid Necrosis in Keratinocytes by a STAT3-Dependent Mechanism

PubMed Central

He, Yong; Fisher, Robert; Chowdhury, Soma; Sultana, Ishrat; Pereira, Claudia P.; Bray, Mike; Reed, Jennifer L.

2014-01-01

Rationale Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens. Methods To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin. Results Mice treated topically with a STAT3 inhibitor (Stattic) developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3. Conclusions Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus. PMID:25419841

Transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications.

PubMed

Said, Maria A; Haile, Charles; Palabindala, Venkataraman; Barker, Naomi; Myers, Robert; Thompson, Ruth; Wilson, Lucy; Allan-Martinez, Frances; Montgomery, Jay; Monroe, Benjamin; Tack, Danielle; Reynolds, Mary; Damon, Inger; Blythe, David

2013-12-01

Severe adverse events, including eczema vaccinatum (EV), can result after smallpox vaccination. Persons at risk for EV include those with underlying dermatologic conditions, such as atopic dermatitis. We investigated a case of vaccinia infection, possibly acquired during sexual contact with a recently vaccinated military service member, in a female Maryland resident with atopic dermatitis. The U.S. Department of Defense's Vaccine Healthcare Centers Network (VHCN) and the Centers for Disease Control and Prevention (CDC) worked in conjunction with the patient's physician and the Maryland Department of Health and Mental Hygiene (DHMH) to confirm the diagnosis, ensure treatment, and prevent further transmission. Specimens collected from the patient were tested at the DHMH laboratories and were positive by real-time polymerase chain reaction for nonvariola orthopoxvirus. Testing at the CDC verified the presence of vaccinia-specific DNA signatures. Continuing spread of the patient's lesions led to the administration of vaccinia immune globulin and strict infection control measures to prevent tertiary transmission to vulnerable family members, also with atopic dermatitis. VHCN contacted the service member to reinforce vaccination site care and hygiene. This case underscores the importance of prevaccination education for those receiving the smallpox vaccine to protect contacts at risk for developing severe adverse reactions. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Eradication of infectious diseases in heterogeneous populations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Travis, C.C.; Lenhart, S.M.

1987-04-01

A model is presented of infectious disease in heterogeneous populations, which allows for variable intra- to intergroup contact ratios. The authors give necessary and sufficient conditions for disease eradication by means of vaccination. Smallpox is used as an illustrative example.

A Global Perspective on Vaccine Safety and Public Health: The Global Advisory Committee on Vaccine Safety

PubMed Central

Folb, Peter I.; Bernatowska, Ewa; Chen, Robert; Clemens, John; Dodoo, Alex N. O.; Ellenberg, Susan S.; Farrington, C. Patrick; John, T. Jacob; Lambert, Paul-Henri; MacDonald, Noni E.; Miller, Elizabeth; Salisbury, David; Schmitt, Heinz-J.; Siegrist, Claire-Anne; Wimalaratne, Omala

2004-01-01

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles–mumps–rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines. PMID:15514229

Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

ERIC Educational Resources Information Center

Pratt, David

1999-01-01

Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

[Epidemics and disease during the Revolution Period in Mexico].

PubMed

Sanfilippo-Borrás, José

2010-01-01

The health condition in Mexico was bad around de beginning of the revolutionary period. The movement of troops led the development of epidemics like yellow fever, typhus, smallpox, and influenza that were enhance with natural disasters and hunger in whole country, from cost to cost and in the north big cities like Monterrey, Guadalajara and Saltillo. Doctor Liceaga conducted a well planned campaign against yellow fever eradicating water stagnant deposits in order to combat the vector transmission, the Aedes aegypti, mosquito with satisfactory results. The first smallpox epidemic in the XX Century in Mexico was in 1916. The Mexican physicians used the smallpox vaccine against this epidemic. An American physician named Howard Taylor Ricketts arrived to Mexico for studying the typhus transmission. Accidentally he had been infected and finally, he died from typhus. Definitively, the epidemics predominate along de revolutionary period in Mexico.

Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory

PubMed Central

Torres, Alice A.; Smith, Geoffrey L.

2018-01-01

The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described. The ultimate goal is to develop safer and more immunogenic VACV vaccines that induce long-lasting immunological memory. PMID:29495547

21 CFR 610.12 - Sterility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Factor, Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood Cells, Anti-Human Globulin, and Blood Grouping Reagents. (2) A manufacturer is not required to comply with the... the test is capable of reliably and consistently detecting the presence of viable contaminating...

21 CFR 610.12 - Sterility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Factor, Platelets, Red Blood Cells, Plasma, Source Plasma, Smallpox Vaccine, Reagent Red Blood Cells, Anti-Human Globulin, and Blood Grouping Reagents. (2) A manufacturer is not required to comply with the... the test is capable of reliably and consistently detecting the presence of viable contaminating...

Adverse Events Post Smallpox-Vaccination: Insights from Tail Scarification Infection in Mice with Vaccinia virus

PubMed Central

Mota, Bruno E. F.; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M. Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A.; Vieira, Leda Q.; da Fonseca, Flávio G.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Damon, Inger K.; Kroon, Erna G.

2011-01-01

Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1 −/−) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1 −/− with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1 −/−, and passive transfer of WT T cells to Rag1 −/− animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify individuals with higher risk of complications after infection with poxvirus. PMID:21526210

Public fear of vaccination: separating fact from fiction.

PubMed

Amanna, Ian; Slifka, Mark K

2005-01-01

During the last two centuries, the world has seen a substantial increase in the number and availability of vaccines for the prevention of infectious disease. Smallpox vaccine remains the most celebrated vaccine-related achievement in human history, but worldwide reductions in many other diseases including measles, mumps, rubella, polio, diphtheria, and whooping cough (Bordetella pertussis) also illustrate the power of vaccination in controlling outbreaks of contagious diseases. Ironically, as advances in vaccination successfully limit disease outbreaks, the impact that these infectious agents once had on society becomes marginalized. Public confidence in vaccination may erode because of real or perceived risks associated with immunization, and this in turn may lead to lower vaccination coverage and loss of herd immunity. Here, we will discuss some of the elements associated with public perceptions and fear of vaccination and place these into the context of how deadly several vaccine-preventable childhood diseases can be if vaccination coverage is insufficient.

Vaccine herd effect

PubMed Central

Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

2011-01-01

Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines. PMID:21604922

Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Hua-Poo; Golden, Joseph W.; Gittis, Apostolos G.

2007-11-25

Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizingmore » activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics.« less

Infection prevention and mass vaccination training for U.S. point of dispensing staff and volunteers: a national study.

PubMed

Rebmann, Terri; Loux, Travis M; Zink, Thomas K; Swick, Zachary; Wakefield, Mary

2015-03-01

Points of dispensing (PODs) are deployed for medical countermeasure mass dispensing. However, infection prevention and vaccine administration pre-event training offered and just-in-time (JIT) education planned for POD workers have not been assessed. Disaster planners were sent an online questionnaire in 2013. McNemar tests compared training offered to staff versus volunteers and pre-event training versus JIT training. In total, 301 disaster planners participated. The most frequent pre-event training included hand hygiene (59.1% and 28.0%) and personal protective equipment (PPE) selection (52.1% and 24.1%) for staff and volunteers, respectively. Few provided pre-event training on the cold chain technique (14.8% and 5.1%) or smallpox vaccine administration (4.7% and 2.3%) for staff or volunteers. For all topics except smallpox vaccine administration, more staff than volunteers received pre-event training (P < .01). The most frequent planned JIT training includes hand hygiene (79.8% and 73.5%) and PPE selection (79.4% and 70.0%) to staff and volunteers. For all topics, more JIT education is planned for staff than volunteers (P < .001). More JIT training is planned than has been given pre-event for all topics (P < .001). More pre-event training is needed on infection prevention and vaccine administration to ensure safe and successful POD deployment. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia virus is isolated from the central nervous system. Manifestations usually occur abruptly and may include fever... spinal cord (myelitis) such as paralysis or meningismus. Long term central nervous system impairments...

Myocardial complications of immunisations.

PubMed

Helle, E P; Koskenvuo, K; Heikkilä, J; Pikkarainen, J; Weckström, P

1978-10-01

Immunisation may induce myocardial complications. In this pilot study clinical, electrocardiographic, chemical and immunological findings have been studied during a six weeks' follow-up after routine immunisation (mumps, polio, tetanus, smallpox, diphtheria and type A meningococcal disease) among 234 Finnish conscripts at the beginning of their military service. Serial pattern of ECG changes suggestive of myocarditis was recorded in eight of the 234 conscripts one to two weeks after vaccination against smallpox and diphtheria. Changes were mainly minor ST segment elevations and T wave inversions and usually they disappeared in a few weeks. The ECG positives more often had a history of atopy, and their mean body temperatures and heart rates after the vaccinations were higher than among the other subjects (p less than 0.01). However, clinical myocarditis was never noted, nor were immunological or enzymological changes different among the ECG positives. Thus in 3% of the study population, evidence of postvaccinal myocarditis was noted, based on serial ECG patterns, but without any other evidence of cardiac disease.

Application of pharmacogenomics to vaccines

PubMed Central

Poland, Gregory A; Ovsyannikova, Inna G; Jacobson, Robert M

2009-01-01

The field of pharmacogenomics and pharmacogenetics provides a promising science base for vaccine research and development. A broad range of phenotype/genotype data combined with high-throughput genetic sequencing and bioinformatics are increasingly being integrated into this emerging field of vaccinomics. This paper discusses the hypothesis of the ‘immune response gene network’ and genetic (and bioinformatic) strategies to study associations between immune response gene polymorphisms and variations in humoral and cellular immune responses to prophylactic viral vaccines, such as measles–mumps–rubella, influenza, HIV, hepatitis B and smallpox. Immunogenetic studies reveal promising new vaccine targets by providing a better understanding of the mechanisms by which gene polymorphisms may influence innate and adaptive immune responses to vaccines, including vaccine failure and vaccine-associated adverse events. Additional benefits from vaccinomic studies include the development of personalized vaccines, the development of novel vaccines and the development of novel vaccine adjuvants. PMID:19450131

Vaccine Therapy for HIV: A Historical Review of the Treatment of Infectious Diseases by Active Specific Immunization with Microbe-Derived Agents

DTIC Science & Technology

1993-01-01

with tuberculosis induced an inflammatory response in affected tissues, and advocated "tuberculin therapy". Sir Almoth Wright in the early 20th...inoculation of tuberculin into patients with tuberculosis Other research groups have recently tried similar induced an inflammatory response in...THERAPY FOR TUBERCULOSIS (1890-191t) smallpox prompted searches for vaccines against other diseases. In 1850 the quixotic French physician While Pasteur

Microbial Scourges and Their Impact on Health.

ERIC Educational Resources Information Center

Howell, Dennis G.; Soltys, Marian A.

1982-01-01

A review of great epidemics (rat-borne, plague, smallpox, cholera, influenza, rabies, tuberculosis) reveals the devastation they have caused. Success in the battle against these is being won through hygiene, sanitation, vector control, and vaccines, especially since microbiology has provided a rational understanding of the diseases. (Author/JN)

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection.

PubMed

Kaminsky, Lauren W; Sei, Janet J; Parekh, Nikhil J; Davies, Michael L; Reider, Irene E; Krouse, Tracy E; Norbury, Christopher C

2015-10-01

Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replication, reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an orthopoxvirus that naturally infects the mouse, spreads systemically from the peripheral site of infection and results in death of susceptible mice. While phagocytic cells have a requisite role in the response to ECTV, the requirement for individual myeloid cell populations during acute immune responses to peripheral viral infection is unclear. In this study, a variety of myeloid-specific depletion methods were used to dissect the roles of individual myeloid cell subsets in the survival of ECTV infection. We showed that DC are the primary producers of type I interferons (T1-IFN), requisite cytokines for survival, following ECTV infection. DC, but not macrophages, monocytes, or granulocytes, were required for control of the virus and survival of mice following ECTV infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid-resident DC subset (CD8α(+) DC) alone did not confer lethal susceptibility to ECTV. However, the function of at least one of the pDC or CD8α(+) DC subsets is required for survival of ECTV infection, as mice depleted of both populations were susceptible to ECTV challenge. The presence of at least one of these DC subsets is sufficient for cytokine production that reduces ECTV replication and virus spread, facilitating survival following infection. Prior to the eradication of variola virus, the orthopoxvirus that causes smallpox, one-third of infected people succumbed to the disease. Following successful eradication of smallpox, vaccination rates with the smallpox vaccine have significantly dropped. There is now an increasing incidence of zoonotic orthopoxvirus infections for which there are no effective treatments. Moreover, the safety of the smallpox vaccine is of great concern, as complications may arise, resulting in morbidity. Like many viruses that cause significant human diseases, orthopoxviruses spread from a peripheral site of infection to become systemic. This study elucidates the early requirement for innate immune cells in controlling a peripheral infection with ECTV, the causative agent of mousepox. We report that there is redundancy in the function of two innate immune cell subsets in controlling virus spread early during infection. The viral control mediated by these cell subsets presents a potential target for therapies and rational vaccine design. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Potent Neutralization of Vaccinia Virus by Divergent Murine Antibodies Targeting a Common Site of Vulnerability in L1 Protein

PubMed Central

Kaever, Thomas; Meng, Xiangzhi; Matho, Michael H.; Schlossman, Andrew; Li, Sheng; Sela-Culang, Inbal; Ofran, Yanay; Buller, Mark; Crump, Ryan W.; Parker, Scott; Frazier, April; Crotty, Shane; Zajonc, Dirk M.; Peters, Bjoern

2014-01-01

ABSTRACT Vaccinia virus (VACV) L1 is an important target for viral neutralization and has been included in multicomponent DNA or protein vaccines against orthopoxviruses. To further understand the protective mechanism of the anti-L1 antibodies, we generated five murine anti-L1 monoclonal antibodies (MAbs), which clustered into 3 distinct epitope groups. While two groups of anti-L1 failed to neutralize, one group of 3 MAbs potently neutralized VACV in an isotype- and complement-independent manner. This is in contrast to neutralizing antibodies against major VACV envelope proteins, such as H3, D8, or A27, which failed to completely neutralize VACV unless the antibodies are of complement-fixing isotypes and complement is present. Compared to nonneutralizing anti-L1 MAbs, the neutralization antibodies bound to the recombinant L1 protein with a significantly higher affinity and also could bind to virions. By using a variety of techniques, including the isolation of neutralization escape mutants, hydrogen/deuterium exchange mass spectrometry, and X-ray crystallography, the epitope of the neutralizing antibodies was mapped to a conformational epitope with Asp35 as the key residue. This epitope is similar to the epitope of 7D11, a previously described potent VACV neutralizing antibody. The epitope was recognized mainly by CDR1 and CDR2 of the heavy chain, which are highly conserved among antibodies recognizing the epitope. These antibodies, however, had divergent light-chain and heavy-chain CDR3 sequences. Our study demonstrates that the conformational L1 epitope with Asp35 is a common site of vulnerability for potent neutralization by a divergent group of antibodies. IMPORTANCE Vaccinia virus, the live vaccine for smallpox, is one of the most successful vaccines in human history, but it presents a level of risk that has become unacceptable for the current population. Studying the immune protection mechanism of smallpox vaccine is important for understanding the basic principle of successful vaccines and the development of next-generation, safer vaccines for highly pathogenic orthopoxviruses. We studied antibody targets in smallpox vaccine by developing potent neutralizing antibodies against vaccinia virus and comprehensively characterizing their epitopes. We found a site in vaccinia virus L1 protein as the target of a group of highly potent murine neutralizing antibodies. The analysis of antibody-antigen complex structure and the sequences of the antibody genes shed light on how these potent neutralizing antibodies are elicited from immunized mice. PMID:25031354

Study of adverse events following immunisation with universal and newer vaccines in the Serampore IMA Child Clinic over a period of 7 years.

PubMed

Das, Pradip Kumar

2013-04-01

Immunisation is an important part of childcare practice. It is one of the most beneficial and cost effective measures for the prevention of diseases. From the previous retrospective studies, it was evident that smallpox has been completely eradicated throughout now-a-days with the wholehearted and sincere efforts of healthcare providers by applying efficient and safe vaccine against smallpox, same is true also to polio which is now close to worldwide eradication and measles and rubella are no longer endemic in certain parts of the world. Not only has that with the introduction of safer and more efficient newer vaccines, the incidence of most other vaccine preventable disease of childhood also reduced considerably. The aim of the present study is to estimate the incidence and clinical presentation of adverse events following immunisation with universal and newer vaccines for a period of seven years using prospective active surveillance. Children under the age of 7 years were taken for universal and newer scheduled vaccinations given in the Serampore IMA Child Clinic under the supervision of the clinicians maintaining strictly the guidelines of Expanded Programme of Immunisation (Government of India). This study of adverse events following immunisation in the Serampore IMA Child Clinic confirms that the adverse events such as fever (0.37%), pain and swelling at the site of injection (0.32%0, urticarial rash (0.02%), anaphylactic shock (0.003%) are negligible. There were only two reports of anaphylaxis following preschool and infant schedule vaccines, including measles, mumps and rubella (MMR), Haemophilus influenzae type B vaccines and typhoid vaccines in approximately 52,000 infants received over a period of 7 years starting from 1st April, 2005 to 31st March, 2012 and there were no deaths or longterm effects reported during the post follow-up period in the Serampore IMA Child Clinic.

From empiricism to rational design: a personal perspective of the evolution of vaccine development.

PubMed

De Gregorio, Ennio; Rappuoli, Rino

2014-07-01

Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

Challenges and solutions for a rational vaccine design for TB-endemic regions.

PubMed

Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

2015-01-01

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

Maintaining an Operational U.S. Army Reserve through Medical Readiness

DTIC Science & Technology

2012-03-07

sometimes referred to as “flagged” vaccines are those required for one’s occupation (e.g., rabies, typhoid , hepatitis B, etc.) or specific for a planned...operation due to location or threat (e.g., anthrax, smallpox, Japanese encephalitis, yellow fever , etc.). While important, these will not be

[Should the human smallpox virus (variola) be destroyed?].

PubMed

Tryland, Morten

2004-10-21

Smallpox, caused by variola virus, was a terror for civilizations around the world for more than 3000 years. Although the disease is eradicated, hundreds of variola virus isolates are kept in two WHO-collaborating facilities, one in USA and one in Russia. In spite of several agreements on destruction, it is now doubtful that these virus isolates will be destroyed. Variola virus may exist in other places and may be used as a biological weapon in war or for terror. Further research on variola virus is thus essential in order to achieve a better understanding of the pathogenicity of the virus and to develop new anti-variola virus vaccines and antiviral drugs.

The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox.

PubMed

Koblentz, Gregory D

In March 2017, the American biotech company Tonix announced that a Canadian scientist had synthesized horsepox virus as part of a project to develop a safer vaccine against smallpox. The first de novo synthesis of an orthopoxvirus, a closely related group of viruses that includes horsepox and the variola virus that causes smallpox, crosses an important Rubicon in the field of biosecurity. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past 40 years by the extreme difficulty of obtaining variola virus and the availability of effective medical countermeasures. The techniques demonstrated by the synthesis of horsepox have the potential to erase both of these barriers. The primary risk posed by this research is that it will open the door to the routine and widespread synthesis of other orthopoxviruses, such as vaccinia, for use in research, public health, and medicine. The normalization and globalization of orthopoxvirus synthesis for these beneficial applications will create a cadre of laboratories and scientists that will also have the capability and expertise to create infectious variola virus from synthetic DNA. Unless the safeguards against the synthesis of variola virus are strengthened, the capability to reintroduce smallpox into the human population will be globally distributed and either loosely or completely unregulated, providing the foundation for a disgruntled or radicalized scientist, sophisticated terrorist group, unscrupulous company, or rogue state to recreate one of humanity's most feared microbial enemies. The reemergence of smallpox-because of a laboratory accident or an intentional release-would be a global health disaster. International organizations, national governments, the DNA synthesis industry, and the synthetic biology community all have a role to play in devising new approaches to preventing the reemergence of smallpox.

Prospects for new viral vaccines.

PubMed

Marmion, B P

1980-08-11

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

Political epidemiology: strengthening socio-political analysis for mass immunisation - lessons from the smallpox and polio programmes.

PubMed

Taylor, S

2009-01-01

Control and reduction of infectious diseases is a key to attaining the Millennium Development Goals. An important element of this work is the successful immunisation, especially in resource-poor countries. Mass immunisation, most intensively in the case of eradication, depends on a combination of reliable demand (e.g. public willingness to comply with the vaccine protocol) and effective supply (e.g. robust, generally state-led, vaccine delivery). This balance of compliance and enforceability is, quintessentially, socio-political in nature - conditioned by popular perceptions of disease and risk, wider conditions of economic development and poverty, technical aspects of vaccine delivery, and the prevailing international norms regarding power relations between states and peoples. In the past 100 years, three out of six disease eradication programmes have failed. The explanations for failure have focused on biotechnical and managerial or financial issues. Less attention is paid to socio-political aspects. Yet socio-political explanations are key. Eradication is neither inherently prone to failure, nor necessarily doomed in the case of polio. However, eradication, and similar mass immunisation initiatives, which fail to address social and political realities of intervention may be. A comparison of the smallpox and polio eradication programmes illustrates the importance of disease-specific socio-political analysis in programme conceptualisation, design, and management.

Governing through time: preparing for future threats to health and security.

PubMed

Samimian-Darash, Limor

2011-09-01

During preparations for the Second Gulf War, Israel considered universal smallpox vaccination. In doing so, it faced a problem: how to legitimise carrying out a security action against an uncertain future danger (smallpox pandemic), when this action carried specific, known risks (vaccine complications). To solve this problem, the Israeli preparedness system created a new domain through which the security action could reach its goal with minimum risk: first responders (a group of medical personnel and security forces). First-responder vaccination represents a shift in the form of 'securing health' and in the governmental technology applied to this goal, in which past, present, and future occurrences are governed to enable the execution of a security action. Through this practice, risks are not located in the present or in the future but in a 'shared' temporal space and thus can be seen as existing simultaneously. Preparedness for emerging future biological events, then, involves more than questioning how the future is contingent on the present and how the present is contingent on the future's perception; it also recognises the need for a new time positioning that allows operating on both present and future risks simultaneously. Governing these risks, then, means governing through time. © 2011 The Author. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

What the world's religions teach, applied to vaccines and immune globulins.

PubMed

Grabenstein, John D

2013-04-12

For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about medical products, explain facts about content and processes, and suggest further dialog with informed religious leaders. Key considerations for observant believers for each populous religion are described. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects.

PubMed

Greenberg, Richard N; Hay, Christine M; Stapleton, Jack T; Marbury, Thomas C; Wagner, Eva; Kreitmeir, Eva; Röesch, Siegfried; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P; Schmidt, Darja; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

2016-01-01

Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18-55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. ClinicalTrials.gov NCT00857493.

The Changing World of Childhood Immunizations

ERIC Educational Resources Information Center

Graville, Iris

2010-01-01

Theories and practices in early childhood education continually evolve, and the same is true in the health field. Such change is especially apparent in the area of childhood immunizations. Since vaccination to prevent smallpox was first started in the late 1700s, recommendations for which immunizations to give and when to give them have been…

ACAM2000(TM): The New Smallpox Vaccine for United States Strategic National Stockpile

DTIC Science & Technology

2010-01-01

1963–1968. BMC Public Health. 2003;3:26. 36. Morgan J, Roper MH, Sperling L, et al. Myocarditis, pericarditis, and dilated cardiomyopathy after...51. von Landenberg P, Lehmann HW, Modrow S. Human parvovirus B19 infection and antiphospholipid antibodies. Autoimmun Rev. 2007;6(5):278–285. 52

Pregnancy, Birth, and Infant Health Outcomes from the National Smallpox Health Vaccine in Pregnancy Registry, 2003-2006

DTIC Science & Technology

2008-01-01

PREGNANCY REGISTRY TEAM From the US Department of Defense: Ava Conlin, Brianna Alexander, Rosha Aran- Loach , Katherine Campbell, Shirley Chow, Renata Engler...Sonja S. Hutchins, Kristin Ken - yan, Sheryl B. Lyss, and Joseph Mulinare. Acknowledgments We gratefully acknowledge the support of all of the

Bleeding for the Village: Success or Failure in the Hands of Local Powerbrokers

DTIC Science & Technology

2012-06-01

only by the energy of the projectile, but also by potentially mortal infection, far from hospital care. I, however, was lucky. Thanks to the...disposal systems, and vaccines for malaria, smallpox , cholera, and typhoid for their communities.38 The same is dynamic is cited in Baker’s

Live attenuated vaccines: Historical successes and current challenges.

PubMed

Minor, Philip D

2015-05-01

Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future.

PubMed

Patel, Manish; Cochi, Stephen

2017-07-01

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.

PubMed

Rosengard, Ariella M; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-06-25

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30-40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges.

Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement

PubMed Central

Rosengard, Ariella M.; Liu, Yu; Nie, Zhiping; Jimenez, Robert

2002-01-01

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30–40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges. PMID:12034872

76 FR 62306 - Countermeasures Injury Compensation Program (CICP): Administrative Implementation, Final Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... respirators, Respiratory support devices, Ventilators, Anthrax, Smallpox, Botulism, Acute radiation syndrome...] and Relenza[supreg] when used for pandemic purposes; (5) smallpox countermeasures; (6) acute radiation syndrome countermeasures; (7) pandemic influenza diagnostics, personal respiratory devices, and respiratory...

Vaccinia Virus: A Tool for Research and Vaccine Development

NASA Astrophysics Data System (ADS)

Moss, Bernard

1991-06-01

Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

A New Document on Smallpox Vaccination.

PubMed

Tayarani-Najaran, Zahra; Tayarani-Najaran, Nilufar; Sahebkar, Amirhossein; Emami, Seyed Ahmad

2016-12-01

Modern medicine owes much to the invaluable heritage of the practices of past generations and their achievements that have now become medical rules. In the case of vaccination, there is evidence that the nomads of Baluchistan (Southeast Iran) demonstrated natural immunization against cowpox, a practice that was later introduced to the medical community by Edward Jenner. Although the discoveries of scientists cannot be ignored, they are certainly based on the traditional and indigenous experiences that have been transferred from generation to generation until reaching us. Copyright © 2016. Published by Elsevier B.V.

ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation.

PubMed

Berhanu, Aklile; King, David S; Mosier, Stacie; Jordan, Robert; Jones, Kevin F; Hruby, Dennis E; Grosenbach, Douglas W

2009-12-01

Orthopoxvirus infections, such as smallpox, can lead to severe systemic disease and result in considerable morbidity and mortality in immunologically naïve individuals. Treatment with ST-246, a small-molecule inhibitor of virus egress, has been shown to provide protection against severe disease and death induced by several members of the poxvirus family, including vaccinia, variola, and monkeypox viruses. Here, we show that ST-246 treatment not only results in the significant inhibition of vaccinia virus dissemination from the site of inoculation to distal organs, such as the spleen and liver, but also reduces the viral load in organs targeted by the dissemination. In mice intranasally infected with vaccinia virus, virus shedding from the nasal and lung mucosa was significantly lower (approximately 22- and 528-fold, respectively) upon ST-246 treatment. Consequently, virus dissemination from the nasal site of replication to the lung also was dramatically reduced, as evidenced by a 179-fold difference in virus levels in nasal versus bronchoalveolar lavage. Furthermore, in ACAM2000-immunized mice, vaccination site swabs showed that ST-246 treatment results in a major (approximately 3,900-fold by day 21) reduction in virus detected at the outside surfaces of lesions. Taken together, these data suggest that ST-246 would play a dual protective role if used during a smallpox bioterrorist attack. First, ST-246 would provide therapeutic benefit by reducing the disease burden and lethality in infected individuals. Second, by reducing virus shedding from those prophylactically immunized with a smallpox vaccine or harboring variola virus infection, ST-246 could reduce the risk of virus transmission to susceptible contacts.

Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection

PubMed Central

Knitlova, Jarmila; Hajkova, Vera; Voska, Ludek; Elsterova, Jana; Obrova, Barbora; Melkova, Zora

2014-01-01

Smallpox vaccine based on live, replicating vaccinia virus (VACV) is associated with several potentially serious and deadly complications. Consequently, a new generation of vaccine based on non-replicating Modified vaccinia virus Ankara (MVA) has been under clinical development. MVA seems to induce good immune responses in blood tests, but it is impossible to test its efficacy in vivo in human. One of the serious complications of the replicating vaccine is eczema vaccinatum (EV) occurring in individuals with atopic dermatitis (AD), thus excluding them from all preventive vaccination schemes. In this study, we first characterized and compared development of eczema vaccinatum in different mouse strains. Nc/Nga, Balb/c and C57Bl/6J mice were epicutaneously sensitized with ovalbumin (OVA) or saline control to induce signs of atopic dermatitis and subsequently trans-dermally (t.d.) immunized with VACV strain Western Reserve (WR). Large primary lesions occurred in both mock- and OVA-sensitized Nc/Nga mice, while they remained small in Balb/c and C57Bl/6J mice. Satellite lesions developed in both mock- and OVA-sensitized Nc/Nga and in OVA-sensitized Balb/c mice with the rate 40–50%. Presence of mastocytes and eosinophils was the highest in Nc/Nga mice. Consequently, we have chosen Nc/Nga mice as a model of AD/EV and tested efficacy of MVA and Dryvax vaccinations against a lethal intra-nasal (i.n.) challenge with WR, the surrogate of smallpox. Inoculation of MVA intra-muscularly (i.m.) or t.d. resulted in no lesions, while inoculation of Dryvax t.d. yielded large primary and many satellite lesions similar to WR. Eighty three and 92% of mice vaccinated with a single dose of MVA i.m. or t.d., respectively, survived a lethal i.n. challenge with WR without any serious illness, while all Dryvax-vaccinated animals survived. This is the first formal prove of protective immunity against a lethal poxvirus challenge induced by vaccination with MVA in an atopic organism. PMID:25486419

Variola minor in coalfield areas of England and Wales, 1921-34: Geographical determinants of a national smallpox epidemic that spread out of effective control.

PubMed

Smallman-Raynor, Matthew R; Rafferty, Sarah; Cliff, Andrew D

2017-05-01

This paper uses techniques of binary logistic regression to identify the spatial determinants of the last national epidemic of smallpox to spread in England and Wales, the variola minor epidemic of 1921-34. Adjusting for age and county-level variations in vaccination coverage in infancy, the analysis identifies a dose-response gradient with increasing odds of elevated smallpox rates in local government areas with (i) medium (odds ratio [OR] = 5.32, 95% Confidence Interval [95% CI] 1.96-14.41) and high (OR = 11.32, 95% CI 4.20-31.59) coal mining occupation rates and (ii) medium (OR = 16.74, 95% CI 2.24-125.21) and high (OR = 63.43, 95% CI 7.82-497.21) levels of residential density. The results imply that the spatial transmission of variola virus was facilitated by the close spatial packing of individuals, with a heightened transmission risk in coal mining areas of the country. A syndemic interaction between common respiratory conditions arising from exposure to coal dust and smallpox virus transmission is postulated to have contributed to the findings. We suggest that further studies of the geographical intersection of coal mining and acute infections that are transmitted via respiratory secretions are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inactivation of Poxviruses by Upper-Room UVC Light in a Simulated Hospital Room Environment

PubMed Central

McDevitt, James J.; Milton, Donald K.; Rudnick, Stephen N.; First, Melvin W.

2008-01-01

In the event of a smallpox outbreak due to bioterrorism, delays in vaccination programs may lead to significant secondary transmission. In the early phases of such an outbreak, transmission of smallpox will take place especially in locations where infected persons may congregate, such as hospital emergency rooms. Air disinfection using upper-room 254 nm (UVC) light can lower the airborne concentrations of infective viruses in the lower part of the room, and thereby control the spread of airborne infections among room occupants without exposing occupants to a significant amount of UVC. Using vaccinia virus aerosols as a surrogate for smallpox we report on the effectiveness of air disinfection, via upper-room UVC light, under simulated real world conditions including the effects of convection, mechanical mixing, temperature and relative humidity. In decay experiments, upper-room UVC fixtures used with mixing by a conventional ceiling fan produced decreases in airborne virus concentrations that would require additional ventilation of more than 87 air changes per hour. Under steady state conditions the effective air changes per hour associated with upper-room UVC ranged from 18 to 1000. The surprisingly high end of the observed range resulted from the extreme susceptibility of vaccinia virus to UVC at low relative humidity and use of 4 UVC fixtures in a small room with efficient air mixing. Increasing the number of UVC fixtures or mechanical ventilation rates resulted in greater fractional reduction in virus aerosol and UVC effectiveness was higher in winter compared to summer for each scenario tested. These data demonstrate that upper-room UVC has the potential to greatly reduce exposure to susceptible viral aerosols. The greater survival at baseline and greater UVC susceptibility of vaccinia under winter conditions suggest that while risk from an aerosol attack with smallpox would be greatest in winter, protective measures using UVC may also be most efficient at this time. These data may also be relevant to influenza, which also has improved aerosol survival at low RH and somewhat similar sensitivity to UVC. PMID:18781204

New and improved vaccines. Promising weapons against varicella, hepatitis A, and typhoid fever.

PubMed

Conrad, D A; Jenson, H B

1996-10-01

The initial motives behind development of vaccines were to protect against life-threatening infections (eg, rabies, diphtheria), to eradicate sweeping outbreaks of serious diseases (eg, paralytic poliomyelitis, smallpox), and to prevent diseases in a vulnerable population by the immunization of surrogates (eg, rubella immunization to prevent congenital rubella syndrome). Now a fourth motive emerges: prevention of less serious infections to improve quality of life. The advantages of new vaccines and immunization programs should no longer be measured exclusively in terms of the number of lives saved but should take into account direct and indirect cost savings and overall benefit to individual and societal health and well-being. Although varicella and hepatitis A infections can be life-threatening, most cases are self-limited and have no significant sequelae. Immunization is more likely to improve quality of life than to save lives. Vaccination against typhoid remains a potentially lifesaving act in developing nations, but even the newer typhoid vaccines were developed primarily to reduce the frequency and severity of adverse reactions to immunization rather than to improve the protective efficacy of the original heat-phenol inactivated vaccine. Varicella virus vaccine, hepatitis A virus vaccines, and the typhoid polysaccharide Vi capsular vaccine represent important additions to immunization agents. These vaccines are immunogenic, clinically effective, and generally safe, with infrequent and usually mild adverse reactions. Their favorable benefit-risk ratio should encourage their appropriate use. The Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians have already recommended varicella vaccine for universal immunization of children. Formal recommendations that hepatitis A vaccine also be routinely used for all children may be forthcoming in the next few years; in the meantime, persons at high risk should be immunized. Typhoid vaccination will likely continue to be used selectively for those who have significant contact with the organism or those who travel to typhoid-endemic countries.

The personal touch: strategies toward personalized vaccines and predicting immune responses to them

PubMed Central

Kennedy, Richard B.; Ovsyannikova, Inna G.; Lambert, Nathaniel D.; Haralambieva, Iana H.; Poland, Gregory A.

2014-01-01

The impact of vaccines on public health and well-being has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as: hepatitis C, malaria, or tuberculosis, as well as new and re-emerging pathogens for which lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population. PMID:24702429

Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response.

PubMed

Paran, Nir; Lustig, Shlomo; Zvi, Anat; Erez, Noam; Israely, Tomer; Melamed, Sharon; Politi, Boaz; Ben-Nathan, David; Schneider, Paula; Lachmi, Batel; Israeli, Ofir; Stein, Dana; Levin, Reuven; Olshevsky, Udy

2013-07-10

Vaccinia virus protein A33 (A33VACV) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. In this study we show that single-dose vaccination with recombinant Sindbis virus expressing A33VACV, is sufficient to protect mice against lethal challenge with vaccinia virus WR (VACV-WR) and ectromelia virus (ECTV) but not against cowpox virus (CPXV), a closely related orthopoxvirus. Moreover, a subunit vaccine based on the cowpox virus A33 ortholog (A33CPXV) failed to protect against cowpox and only partially protected mice against VACV-WR challenge. We mapped regions of sequence variation between A33VACV and A33CPXVand analyzed the role of such variations in protection. We identified a single protective region located between residues 104-120 that harbors a putative H-2Kd T cell epitope as well as a B cell epitope - a target for the neutralizing antibody MAb-1G10 that blocks spreading of extracellular virions. Both epitopes in A33CPXV are mutated and predicted to be non-functional. Whereas vaccination with A33VACV did not induce in-vivo CTL activity to the predicted epitope, inhibition of virus spread in-vitro, and protection from lethal VACV challenge pointed to the B cell epitope highlighting the critical role of residue L118 and of adjacent compensatory residues in protection. This epitope's critical role in protection, as well as its modifications within the orthopoxvirus genus should be taken in context with the failure of A33 to protect against CPXV as demonstrated here. These findings should be considered when developing new subunit vaccines and monoclonal antibody based therapeutics against orthopoxviruses, especially variola virus, the etiologic agent of smallpox.

Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response

PubMed Central

2013-01-01

Vaccinia virus protein A33 (A33VACV) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. In this study we show that single-dose vaccination with recombinant Sindbis virus expressing A33VACV, is sufficient to protect mice against lethal challenge with vaccinia virus WR (VACV-WR) and ectromelia virus (ECTV) but not against cowpox virus (CPXV), a closely related orthopoxvirus. Moreover, a subunit vaccine based on the cowpox virus A33 ortholog (A33CPXV) failed to protect against cowpox and only partially protected mice against VACV-WR challenge. We mapped regions of sequence variation between A33VACV and A33CPXVand analyzed the role of such variations in protection. We identified a single protective region located between residues 104–120 that harbors a putative H-2Kd T cell epitope as well as a B cell epitope - a target for the neutralizing antibody MAb-1G10 that blocks spreading of extracellular virions. Both epitopes in A33CPXV are mutated and predicted to be non-functional. Whereas vaccination with A33VACV did not induce in-vivo CTL activity to the predicted epitope, inhibition of virus spread in-vitro, and protection from lethal VACV challenge pointed to the B cell epitope highlighting the critical role of residue L118 and of adjacent compensatory residues in protection. This epitope’s critical role in protection, as well as its modifications within the orthopoxvirus genus should be taken in context with the failure of A33 to protect against CPXV as demonstrated here. These findings should be considered when developing new subunit vaccines and monoclonal antibody based therapeutics against orthopoxviruses, especially variola virus, the etiologic agent of smallpox. PMID:23842430

Vaccinations against smallpox and tuberculosis are associated with better long-term survival: a Danish case-cohort study 1971-2010.

PubMed

Rieckmann, Andreas; Villumsen, Marie; Sørup, Signe; Haugaard, Line Klingen; Ravn, Henrik; Roth, Adam; Baker, Jennifer Lyn; Benn, Christine Stabell; Aaby, Peter

2017-04-01

When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population. In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes. A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42). Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

Considerations for setting the specifications of vaccines.

PubMed

Minor, Philip

2012-05-01

The specifications of vaccines are determined by the particular product and its method of manufacture, which raise issues unique to the vaccine in question. However, the general principles are shared, including the need to have sufficient active material to immunize a very high proportion of recipients, an acceptable level of safety, which may require specific testing or may come from the production process, and an acceptable low level of contamination with unwanted materials, which may include infectious agents or materials used in production. These principles apply to the earliest smallpox vaccines and the most recent recombinant vaccines, such as those against HPV. Manufacturing development includes more precise definitions of the product through improved tests and tighter control of the process parameters. Good manufacturing practice plays a major role, which is likely to increase in importance in assuring product quality almost independent of end-product specifications.

42 CFR 102.63 - Documentation a representative filing on behalf of an eligible requester who is a minor or a...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Documentation a representative filing on behalf of an eligible requester who is a minor or a legally incompetent adult must submit. 102.63 Section 102.63 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX...

[AIDS in Russia. It is still possible to stop the epidemic. Interview with Dr. A.P. Koslov].

PubMed

Bertrand, P

1996-01-01

According to A.P. Koslov, president of the Fourth International Conference on AIDS, Cancer, and Associated Diseases held in Russia in 1996, the conference represents the first high level discussion of AIDS risk management in Russia. Russia has a strong potential for development of a vaccine, having been a key player in the smallpox eradication program in the late 1950s. Conditions are difficult at present, but it is possible that Russia will be able to develop a practical vaccine for distribution in the Third World. Efforts to develop an HIV vaccine underway in different countries have been examined, and a list has been compiled of Russian institutions able to participate in HIV vaccine development. International assistance for vaccine development in Russia would help both the medical establishment in Russia, which has suffered because of the economic and social crisis, and the international community. A meeting is planned for December 1996 in St. Petersburg to organize an AIDS control organization for all of Russia. Mobilization of support for AIDS prevention activities is necessary but very difficult. If nothing is done, the epidemic in Ukraine will soon spread to Russia. But Russia and China are among the few countries where an HIV epidemic could still be prevented or stopped. The association in St. Petersburg cooperates with other former Soviet republics in AIDS control activities, although attendance at international meetings and conferences is frequently curtailed for financial reasons.

Birth Defects in Infants Born in 1998-2004 to Men and Women Serving in the US Military During the 1990-1991 Gulf War Era

DTIC Science & Technology

2012-08-18

vaccinations , medication, and pesticides) and the prevalence of birth defects in the chil- dren of male Gulf War veterans. In our study, deploy- ment-specific...Defects Res A Clin Mol Teratol 70:572–579. Reichenberg A, Gross R, Weiser M, et al. 2006. Advancing paternal age and autism . Arch Gen Psychiatry 63...received smallpox vaccine . Birth Defects Res A Clin Mol Teratol 82:533–539. Ryan MA, Pershyn-Kisor MA, Honner WK, et al. 2001. The Department of Defense

THE COURSE OF A SMALLPOX VACCINAL PROCESS AND THE FORMATION OF ANTISMALLPOX IMMUNITY IN RABBITS DUE TO THE EFFECT OF X IRRADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamalyan, L.A.

1961-01-01

A study of vaccination process peculiarities in rabbits, previously irradiated with an x-ray dose of 700 r, shows that the course of the process grows worse, the duration of the locai reaction becomes longer, the disease spreads and some of the animals die. A repeated infection of the rabbits (cutaneous and cerebral) shows that the intensity of antismallpox immunity is lower in irradiated animals than in nonirradiated ones in the case of primary and secondary immurization. A total irradiation suppresses the process of hemagglutination. (auth)

Voluntary Vaccination through Self-organizing Behaviors on Locally-mixed Social Networks.

PubMed

Shi, Benyun; Qiu, Hongjun; Niu, Wenfang; Ren, Yizhi; Ding, Hong; Chen, Dan

2017-06-01

Voluntary vaccination reflects how individuals weigh the risk of infection and the cost of vaccination against the spread of vaccine-preventable diseases, such as smallpox and measles. In a homogeneously mixing population, the infection risk of an individual depends largely on the proportion of vaccinated individuals due to the effects of herd immunity. While in a structured population, the infection risk can also be affected by the structure of individuals' social network. In this paper, we focus on studying individuals' self-organizing behaviors under the circumstance of voluntary vaccination in different types of social networks. Specifically, we assume that each individual together with his/her neighbors forms a local well-mixed environment, where individuals meet equally often as long as they have a common neighbor. We carry out simulations on four types of locally-mixed social networks to investigate the network effects on voluntary vaccination. Furthermore, we also evaluate individuals' vaccinating decisions through interacting with their "neighbors of neighbors". The results and findings of this paper provide a new perspective for vaccination policy-making by taking into consideration human responses in complex social networks.

The Florey lecture, 1983. Biological control, as exemplified by smallpox eradication and myxomatosis.

PubMed

Fenner, F

1983-06-22

Biological control is an important method of dealing with plant and insect pests. The control of rabbits by myxomatosis and the eradication of smallpox by vaccination are unusual examples of biological control, in that they involve a vertebrate and a viral pest respectively. Myxomatosis is a benign disease in Sylvilagus rabbits in South America which is transmitted mechanically by mosquitoes. In the European rabbit, Oryctolagus, which is a pest in Australia and England, the virus from Sylvilagus produces a generalized disease that is almost always lethal. Myxomatosis was deliberately introduced into Australia in 1950 and into Europe in 1952. It was at first spectacularly successful in controlling the rabbit pest, but biological adjustments occurred in the virulence of the virus and the genetic resistances of rabbits. After 30 years of interaction, natural selection has resulted in a balance at a fairly high level of viral virulence. Smallpox has been a major scourge of mankind for over 1500 years. It spread from Asia to Europe in the Middle ages and from Europe to Africa and the Americas in the 15th and 16th centuries. Jenner's cowpox vaccine provided a method of control that reduced the severity of the disease during the 19th century but failed to eliminate the disease from many countries before the 1930s. Thereafter it was eradicated from Europe and North America, but remained endemic in South America, Africa and Asia. In 1967 it was still endemic in 33 countries and W.H.O. established a programme for global eradication within 10 years. The goal was achieved in 1977. Problems of the eradication programme and reasons for its success will be described.

Public health and bioterrorism: renewed threat of anthrax and smallpox.

PubMed

Wallin, Arūne; Luksiene, Zivile; Zagminas, Kestutis; Surkiene, Gene

2007-01-01

Bioterrorism is one of the main public health categorical domains. According to sociological analytics, in postmodern society terrorism is one of the real threats of the 21st century. While rare, the use of biological weapons has a long history. Recently, anthrax has been evaluated as one of the most dangerous biological weapons. Naturally occurring anthrax in humans is a disease acquired from contact with anthrax-infected animals or anthrax-contaminated animal products. Usually anthrax infection occurs in humans by three major routes: inhalational, cutaneous, and gastrointestinal. Inhalational anthrax is expected to account for most serious morbidity and most mortality. The clinical presentation of inhalation anthrax has been described as a two-stage illness. Many factors contribute to the pathogenesis of Bacillus anthracis. Antibiotics, anthrax globulin, corticosteroids, mechanical ventilation, vaccine are possible tools of therapy. Smallpox existed in two forms: variola major, which accounted for most morbidity and mortality, and a milder form, variola minor. Smallpox spreads from person to person primarily by droplet nuclei or aerosols expelled from the oropharynx of infected persons and by direct contact. In the event of limited outbreak with few cases, patients should be admitted to the hospital and confined to rooms that are under negative pressure and equipped with high-efficiency particulate air filtration. In larger outbreaks, home isolation and care should be the objective for most patients. Progress in detection, suitable vaccines, postexposure prophylaxis, infection control, and decontamination might be serious tools in fight against the most powerful biological weapon. To assure that the public health and healthcare system can respond to emergencies, the government should direct resources to strengthen the emergency-response system, create medication stockpiles, and improve the public health infrastructure.

[The royal philanthropic expedition of the vaccine (Xavier de Balmis/Josep Salvany). 1803-1806].

PubMed

Botet, Francesc Asensi

2009-12-01

Six years after Jenner discovered the anti-smallpox vaccine, King Charles IV mandated the initiation of vaccination campaigns throughout his kingdom. The overseas campaign was coordinated by the Valencian military doctor Xavier de Balmis with the aid of the Catalan Josep Salvany. The vaccine was transported to America "in vivo" in 22 children. The expedition departed from La Coruña on November 1806 and arrived to the Venezuelan port of La Guayra where it was split in two: One sub expedition under the order of Josep Salvany, continued by land to Colombia, Ecuador, Peru and Bolivia. Salvany died in the Bolivian city of Cochabamba. The other sub expedition, leaded by Balmis himself, continued by sea to Cuba and Mexico. From Acapulco it arrived to Manila and from there to Macau followed by inland penetration into China.

Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination, and Safety

NASA Astrophysics Data System (ADS)

Moss, Bernard

1996-10-01

Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure--function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

[THERMAL STABILITY AS A PROGNOSTIC INDICATOR OF CONSERVATION OF LIVE EMBRYONIC SMALLPOX VACCINE (TEOVAC) DURING STORAGE].

PubMed

Zhukov, V A; Kokorev, S V; Rogozhkina, S V; Melnikov, D G; Terentiev, A I; Kovalchuk, E A; Vakhnov, E Yu; Borisevich, S V

2016-01-01

Determination of values of coefficients of thermal stability of TEOVac for prognosis of conservation of the vaccine (specific biological activity) during the process of warranty period storage. TEOVac (masticatory tablets) in primary packaging was kept at increased temperature (accelerated and stress-tests) and at the conditions established by PAP for the preparation (long-term tests). Biological activity of the vaccine was determined by titration on 12-day chicken embryos. A correlation between the value of coefficients of thermal stability and conservation of the prepared series of the condition preparation at the final date of storage was experimentally established. Coefficients of thermal stability could be used as a prognostic indicator of quality of the produced pelleted formulation of the preparation for evaluation of conservation of the vaccine during warranty period storage.

Current controversies in the USA regarding vaccine safety.

PubMed

Chatterjee, Archana; O'Keefe, Catherine

2010-05-01

As a result of the vaccines discovered in the 20th Century, parents and many healthcare providers of the 21st Century have limited or no experience with the devastating effects of diseases such as polio, smallpox or measles. Fear of disease has shifted to concerns regarding vaccine safety. Scientific evidence has refuted many of the misconceptions regarding vaccine safety; however, parental refusal of vaccines is increasing. Here we review six of the most prevalent controversies surrounding vaccine safety: the proposed causal relationship between receipt of the measles-mumps-rubella vaccine and autism; thimerosal as a potential trigger for autism; religious objection based on some vaccine viruses being grown in cell lines from aborted fetal tissues; parental worries that use of the human papillomavirus vaccine may lead to youth promiscuity; fears regarding the purported association between pertussis vaccination and adverse neurological outcomes; and concerns regarding too many vaccines overloading or weakening the infant immune system. Healthcare providers are ideally positioned to correct these misconceptions, but they must recognize and acknowledge parents' concerns, educate themselves on the latest scientific research that addresses these, and dedicate sufficient time to discuss vaccine safety with worried parents.

Ontology-Based Vaccine Adverse Event Representation and Analysis.

PubMed

Xie, Jiangan; He, Yongqun

2017-01-01

Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125, 1999).Although vaccine development and administration are tremendously successful and cost-effective practices to human health, no vaccine is 100% safe for everyone because each person reacts to vaccinations differently given different genetic background and health conditions. Although all licensed vaccines are generally safe for the majority of people, vaccinees may still suffer adverse events (AEs) in reaction to various vaccines, some of which can be serious or even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged sword of vaccination remains a concern.To support integrative AE data collection and analysis, it is critical to adopt an AE normalization strategy. In the past decades, different controlled terminologies, including the Medical Dictionary for Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf 20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE) (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from: http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc-products.com/graphics/28010.pdf ), have been developed with a specific aim to standardize AE categorization. However, these controlled terminologies have many drawbacks, such as lack of textual definitions, poorly defined hierarchies, and lack of semantic axioms that provide logical relations among terms. A biomedical ontology is a set of consensus-based and computer and human interpretable terms and relations that represent entities in a specific biomedical domain and how they relate each other. To represent and analyze vaccine adverse events (VAEs), our research group has initiated and led the development of a community-based ontology: the Ontology of Adverse Events (OAE) (He et al., J Biomed Semant 5:29, 2014). The OAE has been found to have advantages to overcome the drawbacks of those controlled terminologies (He et al., Curr Pharmacol Rep :1-16. doi:10.1007/s40495-016-0055-0, 2014). By expanding the OAE and the community-based Vaccine Ontology (VO) (He et al., VO: vaccine ontology. In The 1st International Conference on Biomedical Ontology (ICBO-2009). Nature Precedings, Buffalo. http://precedings.nature.com/documents/3552/version/1 ; J Biomed Semant 2(Suppl 2):S8; J Biomed Semant 3(1):17, 2009; Ozgur et al., J Biomed Semant 2(2):S8, 2011; Lin Y, He Y, J Biomed Semant 3(1):17, 2012), we have also developed the Ontology of Vaccine Adverse Events (OVAE) to represent known VAEs associated with licensed vaccines (Marcos E, Zhao B, He Y, J Biomed Semant 4:40, 2013).In this book chapter, we will first introduce the basic information of VAEs, VAE safety surveillance systems, and how to specifically query and analyze VAEs using the US VAE database VAERS (Chen et al., Vaccine 12(10):960-960, 1994). In the second half of the chapter, we will introduce the development and applications of the OAE and OVAE. Throughout this chapter, we will use the influenza vaccine Flublok as the vaccine example to launch the corresponding elaboration (Huber VC, McCullers JA, Curr Opin Mol Ther 10(1):75-85, 2008). Flublok is a recombinant hemagglutinin influenza vaccine indicated for active immunization against disease caused by influenza virus subtypes A and type B. On January 16, 2013, Flublok was approved by the FDA for the prevention of seasonal influenza in people 18 years and older in the USA. Now, more than 3 years later, an exploration of the reported AEs associated with this vaccine is urgently needed.

Trial watch

PubMed Central

Vacchelli, Erika; Martins, Isabelle; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2012-01-01

Prophylactic vaccination constitutes one of the most prominent medical achievements of history. This concept was first demonstrated by the pioneer work of Edward Jenner, dating back to the late 1790s, after which an array of preparations that confer life-long protective immunity against several infectious agents has been developed. The ensuing implementation of nation-wide vaccination programs has de facto abated the incidence of dreadful diseases including rabies, typhoid, cholera and many others. Among all, the most impressive result of vaccination campaigns is surely represented by the eradication of natural smallpox infection, which was definitively certified by the WHO in 1980. The idea of employing vaccines as anticancer interventions was first theorized in the 1890s by Paul Ehrlich and William Coley. However, it soon became clear that while vaccination could be efficiently employed as a preventive measure against infectious agents, anticancer vaccines would have to (1) operate as therapeutic, rather than preventive, interventions (at least in the vast majority of settings), and (2) circumvent the fact that tumor cells often fail to elicit immune responses. During the past 30 y, along with the recognition that the immune system is not irresponsive to tumors (as it was initially thought) and that malignant cells express tumor-associated antigens whereby they can be discriminated from normal cells, considerable efforts have been dedicated to the development of anticancer vaccines. Some of these approaches, encompassing cell-based, DNA-based and purified component-based preparations, have already been shown to exert conspicuous anticancer effects in cohorts of patients affected by both hematological and solid malignancies. In this Trial Watch, we will summarize the results of recent clinical trials that have evaluated/are evaluating purified peptides or full-length proteins as therapeutic interventions against cancer. PMID:23264902

[Reverend Blicher's difficulties with vaccinations in 1807].

PubMed

Bonderup, Gerda

2011-01-01

Prevention of smallpox was the great goal of the doctors since Jenner had published his discoveries in 1798. They had asked for help and ministers, school teachers, and landlords accepted. In fact, ministers performed one fourth of the vaccinations during the first years. One of them was Reverend Niels Blicher from Jutland, the father of a well known Danish writer. However, he soon ran into difficulties because he could not obtain any vaccine. In 1802 an institute had been founded in Copenhagen to organize vaccination of the children in the city, and to provide vaccine for the rest of the country but when Copenhagen was bombarded in 1807 it became nearly impossible to bring out the vaccine. That, however, did not prevent Rev. Blicher from proceeding: When he was told that a child at a manor 15 km away had been vaccinated, he went there together with two children to have them vaccinated with pus from the child at the manor. When the blisters of "his" children had developed, normally after nine days, he would continue with pus from them.

Mistrust in Medicine: The Rise and Fall of America's First Vaccine Institute.

PubMed

Lanzarotta, Tess; Ramos, Marco A

2018-06-01

In 1813, the American government passed An Act to Encourage Vaccination, the first federal endorsement of a medical practice in American history. The law tasked a federal agent with maintaining a supply of the smallpox vaccine and distributing it nationwide. James Smith, a well-respected physician and proponent of vaccination, was appointed as vaccine agent. Smith was skeptical of claims that only well-trained physicians should be allowed to perform vaccination; he felt it was a simple procedure that should be available to all American citizens. In 1822, he made a tragic error that caused several deaths and left him vulnerable to criticism from political opponents and his medical peers. This ended Smith's professional career and led to the repeal of the act itself. In this article, we use the rise and fall of James Smith to provide a historical perspective on contemporary debates surrounding delayed vaccination schedules. We explain how physicians-in the 19th century and today-have worked to build public trust in vaccination in an American culture suspicious of medical expertise.

THE INFLUENCE PRODUCED BY HIGH GAMMA-RAY DOSES ON SOME PROPERTIES OF THE VIRUSES (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bektemirov, T.A.

1961-10-01

The effects produced by gamma rays on infectious, hemagglutinating, and antigenic properties common to the viruses of sneall-pox vaccine and those of infiuenze (grippe) and poliomyelitis were studied. All the viruses were grown on a monostratal culture of a renal epithelium taken from semians. Complete suppression of the vital activity appeared with a dose of 15 x 10/sup 5/ gm for the virus of influenza, 20 x 10/sup 5/ for the virus of small-pox, and 40 x 10/ sup 5/ for that of poliomyelitis. Hemagglutinins of the infiuenza and smallpox viruses became fulIy destroyed at a dose of 30 xmore » 10/sup 5/ gm. The irradiation caused the antigenic properties of the viruses under study to decline. (auth)« less

Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997.

PubMed Central

Hutin, Y. J.; Williams, R. J.; Malfait, P.; Pebody, R.; Loparev, V. N.; Ropp, S. L.; Rodriguez, M.; Knight, J. C.; Tshioko, F. K.; Khan, A. S.; Szczeniowski, M. V.; Esposito, J. J.

2001-01-01

Human monkeypox is a zoonotic smallpox-like disease caused by an orthopoxvirus of interhuman transmissibility too low to sustain spread in susceptible populations. In February 1997, 88 cases of febrile pustular rash were identified for the previous 12 months in 12 villages of the Katako-Kombe Health Zone, Democratic Republic of Congo (attack rate = 22 per 1,000; case-fatality rate = 3.7%). Seven were active cases confirmed by virus isolation. Orthopoxvirus- neutralizing antibodies were detected in 54% of 72 patients who provided serum and 25% of 59 wild-caught animals, mainly squirrels. Hemagglutination-inhibition assays and Western blotting detected antibodies in 68% and 73% of patients, respectively. Vaccinia vaccination, which protects against monkeypox, ceased by 1983 after global smallpox eradication, leading to an increase in the proportion of susceptible people. PMID:11384521

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.

PubMed

Overton, Edgar Turner; Lawrence, Steven J; Wagner, Eva; Nopora, Katrin; Rösch, Siegfried; Young, Philip; Schmidt, Darja; Kreusel, Christian; De Carli, Sonja; Meyer, Thomas P; Weidenthaler, Heinz; Samy, Nathaly; Chaplin, Paul

2018-01-01

Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts. The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637. Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment. The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA. ClinicalTrials.gov NCT01144637.

Journal of Special Operations Medicine. Volume 5, Edition 4, Fall 2005

DTIC Science & Technology

2005-01-01

Africa (outside of South Africa), South and Central America, and Mexico .12 The prevention of diarrhea involves careful food and drink selection, water...high threat as these particles can stay suspended in the air for prolonged periods. Other diseases such as measles, varicella , influenza, and...individuals should be employed. Numerous vaccines including those for measles, influenza, varicella , meningococcus, and smallpox have been developed

DoD Resource Augmentation for Civilian Consequence Management (DRACCM) Tool

DTIC Science & Technology

2015-07-01

staffing availabilities for the nine regions. Finally, we added options to view IDAC data that had included school closings, vaccinations , antivirals...there is enough critical medical resource at that hospital for a given day. An hospital icon coded yellow means that at least one critical medical...tularemia, Q fever , SEB, anthrax, plague (with contagion), VEE, botulism, brucellosis, glanders, smallpox (with contagion), influenza, cesium, sarin, VX

Dismantling the Taboo against Vaccines in Pregnancy

PubMed Central

de Martino, Maurizio

2016-01-01

Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

Dismantling the Taboo against Vaccines in Pregnancy.

PubMed

de Martino, Maurizio

2016-06-07

Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

Vaccine refusal and the endgame: walking the last mile first.

PubMed

Saint-Victor, Diane S; Omer, Saad B

2013-08-05

As multiple papers within this special issue illustrate, the dynamics of disease eradication are different from disease control. When it comes to disease eradication, 'the last mile is longest'. For social and ecological reasons such as vaccine refusal, further ending incidence of a disease when it has reached low levels is frequently complex. Issues of non-compliance within a target population often influence the outcome of disease eradication efforts. Past eradication efforts confronted such obstacles towards the tail end of the campaign, when disease incidence was lowest. This article provides a comparison of non-compliance within polio, measles and smallpox campaigns, demonstrating the tendency of vaccine refusal to rise as disease incidence falls. In order to overcome one of the most intractable challenges to eradication, future disease eradication efforts must prioritize vaccine refusal from the start, i.e. 'walk the last mile first'.

[Comparison of protective properties of the smallpox DNA-vaccine based on the variola virus A30L gene and its variant with modified codon usage].

PubMed

Maksiutov, R A; Shchelkunov, S N

2011-01-01

Efficacy of candidate DNA-vaccines based on the variola virus natural gene A30L and artificial gene A30Lopt with modified codon usage, optimized for expression in mammalian cells, was tested. The groups of mice were intracutaneously immunized three times with three-week intervals with candidate DNA-vaccines: pcDNA_A30L or pcDNA_A30Lopt, and in three weeks after the last immunization all mice in the groups were intraperitoneally infected by the ectromelia virus K1 strain in 10 LD50 dose for the estimation of protection. It was shown that the DNA-vaccines based on natural gene A30L and codon-optimized gene A30Lopt elicited virus, thereby neutralizing the antibody response and protected mice from lethal intraperitoneal challenge with the ectromelia virus with lack of statistically significant difference.