Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

PubMed

Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

2017-01-01

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Antibody responses to influenza a H1N1 vaccine compared to the circulating strain in influenza vaccine recipients during the 2013/2014 season in North America.

PubMed

Barron, Michelle A; Frank, Daniel N; Claypool, David; Ir, Diana; Ning, Mariangeli F; Curtis, Donna; Weinberg, Adriana

2016-10-01

Influenza strain A/California/07/2009 H1N1 (H1N1-09) reemerged in 2013/2014 as the predominant cause of illness. We sought to determine if antigenic drift may have contributed to the decreased responses to influenza vaccine. Fifty adults who received trivalent inactivated influenza vaccine (IIV3) and 56 children who received live attenuated quadrivalent influenza vaccine (LAIV4) had hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies measured in plasma against H1N1-09 and H1N1 2013/2014 (H1N1-14) influenza. Partial sequencing of the hemagglutinin gene (nt 280-780) was performed on 38 clinical isolates and the vaccine prototype. In IIV3 recipients, HAI and MN titers against H1N1-14 were significantly lower than against H1N1-09 (p<0.0001 and 0.04, respectively). In LAIV4 recipients, only MN titers were significantly lower (p=0.02) for H1N1-09 compared with H1N1-14. A combined analysis showed significantly lower HAI and MN titers for H1N1-14 compared with H1N1-09 (p=0. 016 and 0.008, respectively). All 38 clinical isolates encoded the HA gene K166Q non-synonymous substitution; other non-synonymous substitutions were observed in <10% of the clinical isolates. 2013/2014 IIV3 and LAIV4 recipients had consistently lower MN antibody titers against H1N1-14 compared with H1N1-09. The HA K166Q mutation, located in a neutralizing epitope, probably contributed to these findings. Copyright © 2016 Elsevier B.V. All rights reserved.

Implementation of ERDC HEP Geo-Material Model in CTH and Application

DTIC Science & Technology

2011-11-02

used TARDEC JWL inputs for C4 and Johnson- Cook Strength inputs   TARDEC JC fracture model inputs for 5083 plate changed due to problems seen in...fracture inputs from IMD tests -  LS-DYNA C4 JWL and Johnson-Cook strength inputs used in CTH runs -  Results indicate that TARDEC JC fracture model

Improvements to the Sandia CTH Hydro-Code to Support Blast Analysis and Protective Design of Military Vehicles

DTIC Science & Technology

2014-04-15

used for advertising or product endorsement purposes. 6.0 REFERENCES [1] McGlaun, J., Thompson, S. and Elrick, M. “CTH: A Three-Dimensional Shock-Wave...Validation of a Loading Model for Simulating Blast Mine Effects on Armoured Vehicles,” 7 th International LS-DYNA Users Conference, Detroit, MI 2002. [14

Coherence Imaging Measurements of Impurity Flow in the CTH and W7-X Experiments

NASA Astrophysics Data System (ADS)

Ennis, D. A.; Allen, N. R.; Hartwell, G. J.; Johnson, C. A.; Maurer, D. A.; Allen, S. L.; Samuell, C. M.; Gradic, D.; Konig, R.; Perseo, V.; W7-X Team

2017-10-01

Measurements of impurity ion emissivity and velocity in the Compact Toroidal Hybrid (CTH) experiment are achieved with a new optical coherence imaging diagnostic. The Coherence Imaging Spectroscopy (CIS) technique uses an imaging interferometer of fixed delay to provide 2D spectral images, making it ideal for investigating the non-axisymmetric geometry of CTH plasmas. Preliminary analysis of C III interferograms indicate a net toroidal flow on the order of 10 km/s during the time of peak current. Bench tests using Zn and Cd light sources reveal that the temperature of the interferometer optics must be controlled to within 0.01°C to limit phase drift resulting in artificially measured flow. A new collaboration between Auburn University and the Max-Planck-Institute for Plasma Physics is underway to develop two new coherence imaging instruments for ion impurity flow measurements in orthogonal directions to investigate the 3D physics of the W7-X island divertor during OP1.2. A continuous wave laser tunable over most of the visible region will be incorporated to provide immediate and accurate calibrations of both CIS systems during plasma operations. Work supported by USDoE Grant DE-FG02-00ER54610.

Analysis of impact melt and vapor production in CTH for planetary applications

DOE PAGES

Quintana, S. N.; Crawford, D. A.; Schultz, P. H.

2015-05-19

This study explores impact melt and vapor generation for a variety of impact speeds and materials using the shock physics code CTH. The study first compares the results of two common methods of impact melt and vapor generation to demonstrate that both the peak pressure method and final temperature method are appropriate for high-speed impact models (speeds greater than 10 km/s). However, for low-speed impact models (speeds less than 10 km/s), only the final temperature method is consistent with laboratory analyses to yield melting and vaporization. Finally, a constitutive model for material strength is important for low-speed impacts because strengthmore » can cause an increase in melting and vaporization.« less

Analysis of impact melt and vapor production in CTH for planetary applications

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

Quintana, S. N.; Crawford, D. A.; Schultz, P. H.

This study explores impact melt and vapor generation for a variety of impact speeds and materials using the shock physics code CTH. The study first compares the results of two common methods of impact melt and vapor generation to demonstrate that both the peak pressure method and final temperature method are appropriate for high-speed impact models (speeds greater than 10 km/s). However, for low-speed impact models (speeds less than 10 km/s), only the final temperature method is consistent with laboratory analyses to yield melting and vaporization. Finally, a constitutive model for material strength is important for low-speed impacts because strengthmore » can cause an increase in melting and vaporization.« less

A comparative evaluation of a novel vaccine in APP/PS1 mouse models of Alzheimer's disease.

PubMed

Carrera, Iván; Etcheverría, Ignacio; Fernández-Novoa, Lucía; Lombardi, Valter Ruggero Maria; Lakshmana, Madepalli Krishnappa; Cacabelos, Ramón; Vigo, Carmen

2015-01-01

Immunization against amyloid-beta-peptide (Aβ) has been widely investigated as a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim of developing an active immunogenic vaccine without need of coadjuvant modification for human trials and therefore avoiding such side effects, we designed the Aβ 1-42 vaccine (EB101), delivered in a liposomal matrix, that based on our previous studies significantly prevents and reverses the AD neuropathology, clearing Aβ plaques while markedly reducing neuronal degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1 transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared with the original immunization vaccine cocktail Aβ 42 + CFA/IFA (Freund's adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P) in the immunotherapeutic response. Quantitative analysis of amyloid burden showed a notable decrease in the neuroinflammation reaction against Aβ plaques when S1P was compared with other treatments, suggesting that S1P plays a key role as a neuroprotective agent. Moreover, EB101 immunized mice presented a protective immunogenic reaction resulting in the increase of Aβ-specific antibody response and decrease of reactive glia in the affected brain areas, leading to a Th2 immunological reaction.

Analysis of Multi-Layered Materials Under High Velocity Impact Using CTH

DTIC Science & Technology

2008-03-01

of state . The other relationship deals with the deviatoric stress and is taken care of by the constitutive equations which are discussed in the next...models in CTH decompose the total stress tensor into the spherical and deviatoric parts. The spherical part of the stress tensor is the equation of state ...investigate the effects of wave propagation. Waves in rods are considered to create a state of

Reactogenicity of infant whole cell pertussis combination vaccine compared with acellular pertussis vaccines with or without simultaneous pneumococcal vaccine in the Netherlands.

PubMed

David, Silke; Vermeer-de Bondt, Patricia E; van der Maas, Nicoline A T

2008-10-29

In addition to the routine enhanced passive safety surveillance of the Dutch National Vaccination Programme, RIVM (National Institute for Public Health and the Environment) started a large questionnaire study enrolling approximately 53,000 children from December 2003 until September 2007. We intended to establish accurate frequency estimates for several more severe adverse events and to compare the incidence rates of three different infant vaccines that were used consecutively. Whole cell pertussis (wP) DTP-IPV-Hib vaccine (NVI) was replaced by acellulair pertussis (aP) in 2005, first Infanrix-IPV-Hib (GSK) followed by Pediacel (Sanofi) in 2006. Pneumococcal vaccine, Prevenar (Wyeth), was added for children born from April 2006. Parents returned 28,796 questionnaires (response 54%), 15,069 for whole cell pertussis and 13,727 for acellular pertussis vaccine, including 4485 with pneumococcal vaccine. The OR for reported events was 3-6 for whole cell pertussis vaccine compared with acellular vaccine. This was true for prolonged crying for 3h and more after the first dose (1.5% versus 0.4%; 95 CI 1.1-1.9 and 95% CI 0.2-0.7, respectively), and very high fever of 40.5 degrees C and over following the fourth dose (0.8% versus 0.2%; 95% CI 0.5-1.1 and 0.06-0.3, respectively), while possible febrile convulsions were diagnosed only twice after the fourth dose in the whole cell vaccine group and one after acellular pertussis vaccine. Pallor was significantly more frequent after the first dose of whole cell pertussis than after acellulair pertussis vaccination (18.3% versus 3.4%; 95% CI 17.2-19.5 and 95% CI 2.8-4.0 respectively) Collapse after the first dose was rare in both vaccine groups (5 after whole cell vaccine and 1 after acellular vaccine). The addition of conjugated pneumococcal vaccine did not result in statistically significant increased rates of adverse events in the acellular vaccine group. Whole cell pertussis vaccine showed a significantly higher reactogenicity

Comparing health outcomes and costs of general vaccination with pneumococcal conjugate vaccines in Sweden: a Markov model.

PubMed

By, Asa; Sobocki, Patrik; Forsgren, Arne; Silfverdal, Sven-Arne

2012-01-01

Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio. The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)

PubMed Central

Gambaryan, Alexandra S.; Lomakina, Natalia F.; Boravleva, Elizaveta Y.; Kropotkina, Ekaterina A.; Mashin, Vadim V.; Krasilnikov, Igor V.; Klimov, Alexander I.; Rudenko, Larisa G.

2011-01-01

Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses 6(3), 188–195. Objective  Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Method  Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non‐glycoprotein genes of the experimental live vaccines were from H2N2 cold‐adapted master strain A/Leningrad/134/17/57 (VN‐Len and Ku‐Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN‐Gull and Ku‐Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. Results  All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold‐adapted H1N1 vaccine reduced the mortality near to zero level. Conclusions  The high yield, safety, and protectivity of VN‐Len and Ku‐Len made them promising strains for the production of inactivated and live

Comparative study and evaluation of further attenuated, live measles vaccines alone and in combination with mumps and rubella vaccines.

PubMed

Wegmann, A; Glück, R; Just, M; Mischler, R; Paroz, P; Germanier, R

1986-01-01

The further attenuated Enders (FAE) measles vaccine strain and the Edmonston B-Zagreb (EZ) measles vaccine strain were compared. In VERO-cells plaque sizes of FAE varied between 0.5 and 1 mm, those of EZ between 1 and 2 mm in diameter. The lots available in Switzerland during a 2 year period showed virus titers of 10(3.1) to 10(4.0) TCID50 per dose in the one vaccine (FAE) and of 10(3.1) to 10(4.5) TCID50 per dose in the other (EZ). Clinical investigations were performed with FAE and EZ monovalent and trivalent (measles + mumps + rubella) vaccine preparations. The virus titers of the vaccine lots used were 10(3.1) to 10(4.0) TCID50 per dose. The overall seroconversion rates of 96% to 100% indicate that both types of vaccine have comparable immunization properties. Stability tests demonstrated good stability of both the FAE and the EZ vaccines. Thus conservation at 37 degrees C was possible for 2 and 4 weeks, respectively, and at 41 degrees C for 6 and 6 days, respectively, without undue loss of live virus content (less than 1 log 10). Since the EZ vaccine is derived from human diploid cells, it is particularly suitable for the vaccination of persons with a history of allergy to avian proteins.

Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

PubMed

Frösner, Gert; Steffen, Robert; Herzog, Christian

2009-01-01

Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

[Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

PubMed

Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

2013-01-01

To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

PubMed

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

2016-10-17

Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques.

PubMed

Livingston, Brian D; Little, Stephen F; Luxembourg, Alain; Ellefsen, Barry; Hannaman, Drew

2010-01-22

DNA vaccination is a promising immunization strategy that could be applied in the development of vaccines for a variety of prophylactic and therapeutic indications. Utilizing anthrax protective antigen as a model antigen, we demonstrate that electroporation mediated delivery enhanced the immunogenicity of DNA vaccines in nonhuman primates over 100-fold as compared to conventional intramuscular injection. Two administrations of a DNA vaccine with electroporation elicited anthrax toxin neutralizing antibody responses in 100% of rhesus macaques. Toxin neutralizing antibodies were sustained for the nearly 1-year study duration and were correlated with protection against subsequent lethal Bacillus anthracis spore challenge. Collectively, electroporation mediated DNA vaccination conferred protection comparable to that observed following vaccination with an FDA approved anthrax vaccine.

Sieve analysis in HIV-1 vaccine efficacy trials.

PubMed

Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

2013-09-01

The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

Measurements of W Erosion using UV Emission from DIII-D and CTH

NASA Astrophysics Data System (ADS)

Johnson, Curtis; Ennis, David; Loch, Stuart; Balance, Connor; Victor, Brian; Allen, Steve; Samuell, Cameron; Abrams, Tyler; Unterberg, Ezekial

2017-10-01

of Plasma Facing Components (PFCs) will play a critical role in establishing the performance of reactor-relevant fusion devices, particularly for tungsten (W) divertor targets. Erosion can be diagnosed from spectral line emission together with atomic coefficients representing the `ionizations per photon' (S/XB). Emission from W I is most intense in the UV region. Thus, UV survey spectrometers (200-400 nm) are used to diagnose W PFCs erosion in the DIII-D divertor and from a W tipped probe in the CTH experiment. Nineteen W emission lines in the UV region are identified between the two experiments, allowing for multiple S/XB erosion measurements. Initial W erosion measurements are compared to erosion using the 400.9 nm W I line. Complete UV spectra will be presented and compared to synthetic spectra for varying plasma conditions. Analysis of the metastable states impact on the S/XB will be presented as well as possible electron temperature and density diagnosis from W I line ratios. Work supported by USDOE Grants DE-SC0015877 & DE-FC02-04ER54698.

Effect of Repeated Vaccination With the Same Vaccine Component Against 2009 Pandemic Influenza A(H1N1) Virus.

PubMed

Martínez-Baz, Iván; Casado, Itziar; Navascués, Ana; Díaz-González, Jorge; Aguinaga, Aitziber; Barrado, Laura; Delfrade, Josu; Ezpeleta, Carmen; Castilla, Jesús

2017-03-15

The 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) vaccine component has remained unchanged from 2009. We estimate the effectiveness of current and prior inactivated influenza A(H1N1)pdm09 vaccination from influenza seasons 2010-2011 to 2015-2016. Patients attended with influenza-like illness were tested for influenza. Four periods with continued A(H1N1)pdm09 circulation were included in a test-negative design. We enrolled 1278 cases and 2343 controls. As compared to individuals never vaccinated against influenza A(H1N1)pdm09, the highest effectiveness (66%; 95% confidence interval, 49%-78%) was observed in those vaccinated in the current season who had received 1-2 prior doses. The effectiveness was not statistically lower in individuals vaccinated in the current season only (52%) or in those without current vaccination and >2 prior doses (47%). However, the protection was lower in individuals vaccinated in the current season after >2 prior doses (38%; P = .009) or those currently unvaccinated with 1-2 prior doses (10%; P < .001). Current-season vaccination improved the effect in individuals with 1-2 prior doses and did not modify significantly the risk of influenza in individuals with >2 prior doses. Current vaccination or several prior doses were needed for high protection. Despite the decreasing effect of repeated vaccination, current-season vaccination was not inferior to no current-season vaccination. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Coupling Between CTH and LS-DYNA for Thermal Postprocessing: Application to Propellant Cookoff From a Residual Penetrator

DTIC Science & Technology

2006-09-01

1 1 θα θ ∇= ∂ ∂ t ; 1Ω∈x , 0>t (7) and 2 2 2 2 θα θ ∇= ∂ ∂ t ; 2Ω∈x , 0>t , (8) 12 in which α1 and α2 are the thermal diffusivities of steel and...M30A1, respectively. These are defined by p11 1 1 cρ κ α = (9) and p22 2 2 cρ κ α = . (10) Here, κ1 ad κ2 are the thermal conductivities...Coupling Between CTH and LS-DYNA for Thermal Postprocessing: Application to Propellant Cookoff From a Residual Penetrator by Martin N

Sieve analysis in HIV-1 vaccine efficacy trials

PubMed Central

Edlefsen, Paul T.; Gilbert, Peter B.; Rolland, Morgane

2013-01-01

Purpose of review The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. Recent findings The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 and RV144, led to numerous studies in the last five years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Summary Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons while correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection. PMID:23719202

Prevention of fetal infection in heifers challenged with bovine viral diarrhoea virus type 1a by vaccination with a type 1c or type 1a vaccine.

PubMed

Packianathan, R; Clough, W J; Hodge, A; Holz, D K; Huang, J; Bryant, G L; Colantoni, C

2017-05-01

To evaluate a vaccine containing type 1c bovine viral diarrhoea (BVD) virus for prevention of fetal infection in pregnant heifers when challenged with New Zealand BVD virus type 1a 6 months after vaccination, compared to unvaccinated heifers and heifers vaccinated with a vaccine containing type 1a BVD virus. Fifty five crossbred Friesian heifers, free from BVD virus and antibody, were randomly allocated to three groups. Twenty five heifers were vaccinated twice with a vaccine containing type 1c BVD virus (T1c group), and 10 heifers with a vaccine containing type 1a BVD virus (T1a group), and 20 heifers were unvaccinated (NC group). After oestrus synchronisation the heifers were bred by artificial insemination followed by natural bull mating. Six months after booster vaccination 15 heifers from the T1c group, eight from the T1a group, and 15 from the NC group, were exposed to four calves that were persistently infected with type 1a BVD virus, for 4 weeks. At the beginning of the challenge phase 36/38 heifers were 72-74 days pregnant and 2/38 heifers were approximately 53 days pregnant. Approximately 52 days after the start of the challenge the heifers were subjected to euthanasia and fetal tissues were collected for the detection of BVD virus by ELISA in fetal heart blood and PCR in fetal tissues. Based on PCR results, BVD virus was detected in 15/15 fetuses in the NC group, compared to 4/14 fetuses in the T1c group and 3/8 fetuses in the T1a group. The proportion of BVD virus-positive fetuses was lower in both vaccinated groups compared to the NC group (p<0.002), but there was no difference in proportions between the vaccinated groups (p=1.00). Fetal protection, expressed as the prevented fraction, was 71.4 (95% CI=41.9-91.6)% and 62.5 (95% CI=24.5-91.5)% for the T1c and T1a groups, respectively. The vaccines containing killed type 1c and type 1a BVD viruses significantly reduced fetal infection following challenge with a New Zealand type 1a BVD virus. Prevention

Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine).

PubMed

Gambaryan, Alexandra S; Lomakina, Natalia F; Boravleva, Elizaveta Y; Kropotkina, Ekaterina A; Mashin, Vadim V; Krasilnikov, Igor V; Klimov, Alexander I; Rudenko, Larisa G

2012-05-01

Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level. The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses. © 2011 Blackwell Publishing Ltd.

Public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines compared to trivalent influenza vaccines in Europe.

PubMed

Uhart, Mathieu; Bricout, Hélène; Clay, Emilie; Largeron, Nathalie

2016-09-01

Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs.

Determinants of Parental Acceptance of the H1N1 Vaccine

ERIC Educational Resources Information Center

Hilyard, Karen M.; Quinn, Sandra Crouse; Kim, Kevin H.; Musa, Don; Freimuth, Vicki S.

2014-01-01

Although designated as a high-risk group during the 2009-2010 H1N1 pandemic, only about 40% of U.S. children received the vaccine, a relatively low percentage compared with high-risk groups in seasonal influenza, such as the elderly, whose vaccine rates typically top 70%. To better understand parental decision making and predictors of acceptance…

HIV-1 vaccines

PubMed Central

Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H

2014-01-01

The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure. PMID:24637946

H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines.

PubMed

Wong, Sook-San; DeBeauchamp, Jennifer; Zanin, Mark; Sun, Yilun; Tang, Li; Webby, Richard

2017-01-01

Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.

A(H1N1)pdm09 influenza infection: vaccine inefficiency.

PubMed

Friedman, Nehemya; Drori, Yaron; Pando, Rakefet; Glatman-Freedman, Aharona; Sefty, Hanna; Bassal, Ravit; Stein, Yaniv; Shohat, Tamy; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

2017-05-16

The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015-2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

Comparing the quality of pro- and anti-vaccination online information: a content analysis of vaccination-related webpages.

PubMed

Sak, Gabriele; Diviani, Nicola; Allam, Ahmed; Schulz, Peter J

2016-01-15

The exponential increase in health-related online platforms has made the Internet one of the main sources of health information globally. The quality of health contents disseminated on the Internet has been a central focus for many researchers. To date, however, few comparative content analyses of pro- and anti-vaccination websites have been conducted, and none of them compared the quality of information. The main objective of this study was therefore to bring new evidence on this aspect by comparing the quality of pro- and anti-vaccination online sources. Based on past literature and health information quality evaluation initiatives, a 40-categories assessment tool (Online Vaccination Information Quality Codebook) was developed and used to code a sample of 1093 webpages retrieved via Google and two filtered versions of the same search engine. The categories investigated were grouped into four main quality dimensions: web-related design quality criteria (10 categories), health-specific design quality criteria (3 categories), health related content attributes (12 categories) and vaccination-specific content attributes (15 categories). Data analysis comprised frequency counts, cross tabulations, Pearson's chi-square, and other inferential indicators. The final sample included 514 webpages in favor of vaccination, 471 against, and 108 neutral. Generally, webpages holding a favorable view toward vaccination presented more quality indicators compared to both neutral and anti-vaccination pages. However, some notable exceptions to this rule were observed. In particular, no differences were found between pro- and anti-vaccination webpages as regards vaccination-specific content attributes. Our analyses showed that the overall quality of pro-vaccination webpages is superior to anti-vaccination online sources. The developed coding scheme was proven to be a helpful and reliable tool to judge the quality of vaccination-related webpages. Based on the results, we advance

Acceptance of 2009 H1N1 influenza vaccine among pregnant women in Delaware.

PubMed

Drees, Marci; Johnson, Oluwakemi; Wong, Esther; Stewart, Ashley; Ferisin, Stephanie; Silverman, Paul R; Ehrenthal, Deborah B

2012-04-01

Due to disproportionately high mortality from 2009 H1N1 influenza, pregnant women were given highest priority for H1N1 vaccination. We surveyed postpartum women to determine vaccine uptake and reasons for lack of vaccination. We performed a cross-sectional survey of postpartum women delivering at our institution from February 1 to April 15, 2010. The 12-question survey ascertained maternal characteristics and vaccination concerns. Among 307 postpartum women, 191 (62%) had received H1N1 vaccination and 98 (32%) had declined. Factors associated with H1N1 vaccination included older age (relative risk [RR] 1.3, 95% confidence interval [CI] 1.1 to 1.5 for age ≥35 years compared with 20 to 34 years), at least college education (RR 1.5, 95% CI 1.3 to 1.8), prior influenza vaccination (RR 1.6, 95% CI 1.3 to 2.0), provider recommendation (RR 3.9, 95% CI 2.1 to 7.4), vaccination of family members (RR 1.6, 95% CI 1.3 to 1.9), and receipt of seasonal influenza vaccination (RR 2.2, 95% CI 1.7 to 2.9). Non-Hispanic black women were less likely to have been vaccinated (RR 0.6, 95% CI 0.5 to 0.8) than non-Hispanic white women. Safety concerns were cited by the majority (66%) of nonvaccinated women. H1N1 vaccine uptake among pregnant women was substantially higher than reported influenza vaccination rates during previous seasons. Safety concerns were the major barrier to vaccination. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Associations between health communication behaviors, neighborhood social capital, vaccine knowledge, and parents' H1N1 vaccination of their children.

PubMed

Jung, Minsoo; Lin, Leesa; Viswanath, K

2013-10-01

During the H1N1 pandemic in 2009-10, the vaccination behavior of parents played a critical role in preventing and containing the spread of the disease and the subsequent health outcomes among children. Several studies have examined the relationship between parents' health communication behaviors and vaccinations for children in general. Little is known, however, about the link between parents' health communication behaviors and the vaccination of their children against the H1N1 virus, and their level of vaccine-related knowledge. We drew on a national survey among parents with at least one child less than 18 years of age (n=639) to investigate Parents' H1N1-related health communication behaviors including sources of information, media exposure, information-seeking behaviors, H1N1-related knowledge, and neighborhood social capital, as well as the H1N1 vaccination rates of their children. Findings showed that there is a significant association between the degree at which parents obtained H1N1 vaccination for their children and health communication variables: watching the national television news and actively seeking H1N1 information. And this association was moderated by the extent of the parents' H1N1-related knowledge. In addition, the parents' degree of neighborhood social capital mediated the association between H1N1 knowledge of the parents and H1N1 vaccination acceptance for their children. We found, compared to those with a low-level of neighborhood social capital, parents who have a high-level of neighborhood social capital are more likely to vaccinate their children. These findings suggest that it is necessary to design a strategic health communication campaign segmented by parent health communication behaviors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.

PubMed

Fisker, Ane Bærent; Ravn, Henrik; Rodrigues, Amabelia; Østergaard, Marie Drivsholm; Bale, Carlito; Benn, Christine Stabell; Aaby, Peter

2014-01-23

Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4). In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative Proteome Analysis of Brucella melitensis Vaccine Strain Rev 1 and a Virulent Strain, 16M

PubMed Central

Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A.; Kraycer, Jo Ann; Mujer, Cesar V.; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G.

2002-01-01

The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1. PMID:12193611

Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain, 16M.

PubMed

Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A; Kraycer, Jo Ann; Mujer, Cesar V; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G

2002-09-01

The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1.

2009 H1N1 Flu Vaccine Facts

MedlinePlus

... turn Javascript on. Feature: Flu 2009 H1N1 Flu Vaccine Facts Past Issues / Fall 2009 Table of Contents ... H1N1 flu vaccine. 1 The 2009 H1N1 flu vaccine is safe and well tested. Clinical trials conducted ...

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

PubMed Central

Libraty, Daniel H.; Zhang, Lei; Woda, Marcia; Acosta, Luz P.; Obcena, AnaMae; Brion, Job D.; Capeding, Rosario Z.

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later. PMID:24611083

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines.

PubMed

Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-γ producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later.

Cost-effectiveness analysis of the bivalent compared with the quadrivalent human papillomavirus vaccines in Taiwan.

PubMed

Demarteau, Nadia; Tang, Chao-Hsiun; Chen, Hui-Chi; Chen, Chien-Jen; Van Kriekinge, Georges

2012-01-01

To compare the epidemiological and economic impact of additional cross-protection against oncogenic human papillomavirus (HPV) types beyond 16/18 of the bivalent vaccine (BV) versus protection against nononcogenic HPV types 6/11 of the quadrivalent vaccine (QV) in Taiwan. A lifetime Markov model calibrated to the Taiwanese setting simulated the natural history of low-risk (engendering cervical intraepithelial neoplasia [CIN] 1 and genital warts) and high-risk HPV (engendering CIN1, CIN2/3, and cervical cancer [CC]) infections, screening, and vaccination (100% coverage) for a cohort of 12-year-old girls (N = 153,000). Transition probabilities, costs, and utilities were estimated from published data and expert opinion. Vaccine efficacy was obtained from each vaccine's respective clinical trials. Price-parity and lifelong protection was assumed for both vaccines. The number of CIN lesions, CC cases, CC deaths and genital wart (GW) cases, and quality-adjusted life-years were estimated. Costs and outcomes (discounted at 3% and 1.5%, respectively) were compared from a payer's perspective. The model estimated that the BV led to an additional, undiscounted, 11,484 CIN1, 1,779 (+34.3% vs. QV) CIN2/3, 188 (+29.0% vs. QV) CC, and 69 (+29.0% vs. QV) CC deaths prevented compared with the QV, while the QV prevented 4,150 GW (+71%). This resulted in an additional 768 quality-adjusted life-years (QALY) and 11.6 million new Taiwan dollars costs saved for the BV versus the QV after discounting. Both vaccines have a different epidemiological impact with an increased number of CC-related lesions potentially prevented for the BV because of additional cross-protection. In the Taiwanese setting, HPV mass vaccination using the BV was estimated to dominate vaccination using the QV. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Gaming as a Therapeutic Tool in Adolescence. Experience of Institutional Therapy of CThA, UCL, Brussels, Belgium.

PubMed

Descamps, Guillaume; d'Alcantara, Ann

2016-09-01

This work presents the experience of an Emancipatory action research led at the Therapeutic Center for Adolescents (CThA) at Saint Luc's Clinics (UCL). This research focuses on the practice effects of "Pixels" and "Passerelle" workshops at CThA. It is about the use of video games as a therapeutic tool, mobilizing of the symptomatology of the teenager. "Pixels" workshops use playing according to three specific forms: the paper role-play game, the video game, and the cards playing game. Their specificity is that the participative adult shows a regressive ability strong enough to play with teenagers and is very careful to not interpret what takes place within. "Passerelle" workshops demonstrate the link between the teenager's mind and the use of his own virtual avatar. It allows to evolve from a "play together" to a "talk together", a moment of symbolization and of being able to stand back in regards to his or her own recreational activities. As a discussion, this clinical illustration of Karl recovering from depression and dependency. This setting for speech allowed him to evolve into an impulse mood and to reconnect emotionally.

Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

PubMed

Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

2014-12-12

A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years); Cohort B (≥3 years to <9 years); and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost-Effectiveness of 2009 Pandemic Influenza A(H1N1) Vaccination in the United States

PubMed Central

Prosser, Lisa A.; Lavelle, Tara A.; Fiore, Anthony E.; Bridges, Carolyn B.; Reed, Carrie; Jain, Seema; Dunham, Kelly M.; Meltzer, Martin I.

2011-01-01

Background Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination. Methodology A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted. Results For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery. Conclusions Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial

Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model.

PubMed

Opriessnig, Tanja; Gauger, Phillip C; Gerber, Priscilla F; Castro, Alessandra M M G; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G; Xia, Ming; Jiang, Xi; Tan, Ming

2018-01-01

Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids

Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model

PubMed Central

Gauger, Phillip C.; Gerber, Priscilla F.; Castro, Alessandra M. M. G.; Shen, Huigang; Murphy, Lita; Digard, Paul; Halbur, Patrick G.; Xia, Ming; Jiang, Xi; Tan, Ming

2018-01-01

Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids

Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda

PubMed Central

Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

2016-01-01

The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15–24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01–0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages. PMID:27482705

Seasonal and 2009 H1N1 influenza vaccine uptake, predictors of vaccination and self-reported barriers to vaccination among secondary school teachers and staff

PubMed Central

Painter, Julia E; Sales, Jessica M; Morfaw, Christopher; Jones, LaDawna M; Murray, Dennis; Wingood, Gina M; DiClemente, Ralph J; Hughes, James M

2011-01-01

Objective Teachers, like healthcare workers, may be a strategic target for influenza immunization programs. Influenza vaccination is critical to protect both teachers and the students they come into contact with. This study assessed factors associated with seasonal and H1N1 influenza vaccine uptake among middle- and high-school teachers. Results Seventy-eight percent of teachers who planned to receive seasonal influenza vaccine and 36% of those who planned to receive H1N1 influenza vaccine at baseline reported that they did so. Seasonal vaccine uptake was significantly associated with perceived severity (odds ratio [OR] 1.57, p = 0.05) and self-efficacy (OR 4.46, p = 0.006). H1N1 vaccine uptake was associated with perceived barriers (OR 0.7, p = 0.014) and social norms (OR 1.39, p = 0.05). The number one reason for both seasonal and H1N1 influenza vaccine uptake was to avoid getting seasonal/H1N1 influenza disease. The number one reason for seasonal influenza vaccine refusal was a concern it would make them sick and for H1N1 influenza vaccine refusal was concern about vaccine side effects. Methods Participants were recruited from two counties in rural Georgia. Data were collected from surveys in September 2009 and May 2010. Multivariate logistic regression was used to assess the association between teachers' attitudes toward seasonal and H1N1 influenza vaccination and vaccine uptake. Conclusions There is a strong association between the intention to be vaccinated against influenza (seasonal or 2009 H1N1) and actual vaccination uptake. Understanding and addressing factors associated with teachers' influenza vaccine uptake may enhance future influenza immunization efforts. PMID:21263225

Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

PubMed Central

Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

2014-01-01

The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

Safety of pandemic H1N1 vaccines in children and adolescents.

PubMed

Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam

2011-10-06

During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

PubMed Central

Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.

2016-01-01

Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485

Comparing vaccines: a systematic review of the use of the non-inferiority margin in vaccine trials.

PubMed

Donken, R; de Melker, H E; Rots, N Y; Berbers, G; Knol, M J

2015-03-17

Non-inferiority (NI) randomized controlled trials (RCTs) aim to demonstrate that a new treatment is no worse than a comparator that has already shown its efficacy over placebo within a pre-specified margin. However, clear guidelines on how the NI margin should be determined are lacking for vaccine trials. A difference (seroprevalence/risk) of 10% or a geometric mean titre/concentration (GMT) ratio of 1.5 or 2.0 in antibody levels is implicitly recommended for vaccine trials. We aimed to explore which NI margins were used in vaccine RCTs and how they were determined. A systematic search for NI vaccine RCTs yielded 177 eligible articles. Data were extracted from these articles using a standardized form and included general characteristics and characteristics specific for NI trials. Relations between the study characteristics and the NI margin used were explored. Among the 143 studies using an NI margin based on difference (n=136 on immunogenicity, n=2 on efficacy and n=5 on safety), 66% used a margin of 10%, 23% used margins lower than 10% (range 1-7.5%) and 11% used margins larger than 10% (range 11.5-25%). Of the 103 studies using a NI margin based on the GMT ratio, 50% used a margin of 0.67/1.5 and 49% used 0.5/2.0. As observed, 85% of the studies did not discuss the method of margin determination; and 19% of the studies lacked a confidence interval or p-value for non-inferiority. Most NI vaccine RCTs used an NI margin of 10% for difference or a GMT ratio of 1.5 or 2.0 without a clear rationale. Most articles presented enough information for the reader to make a judgement about the NI margin used and the conclusions. The reporting on the design, margins used and results of NI vaccine trials could be improved; more explicit guidelines may help to achieve this end. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

PubMed

Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

2013-08-01

An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In

Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

PubMed

Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

2015-01-01

As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.

[Attitudes and side effects related to pandemic influenza A (H1N1) vaccination in healthcare personnel].

PubMed

Ormen, Bahar; Türker, Nesrin; Vardar, Ilknur; Kaptan, Figen; El, Sibel; Ural, Serap; Kaya, Fatih; Coşkun, Nejat Ali

2012-01-01

The aims of this study were to evaluate the attitudes towards H1N1 vaccination and to determine the safety and side effects following 2009 pandemic influenza A (H1N1) vaccination. Pandemic influenza vaccine had been administered to the healthcare personnel in our research and training hospital in December 2009. The rate being vaccinated was established as 40% (800/2000). Four months following vaccination, the opinions about vaccination were asked to the healthcare workers, and also side effects were questioned to the vaccinated group. Two different questionnaires (for vaccinated and unvaccinated subjects) were delivered to the volunteers who agreed to participate in the study. Demographic features, reasons related to being vaccinated or not, were questioned. The vaccinated group was also questioned for the presence of chronic diseases, previous vaccinations (pandemic/seasonal influenza), local or systemic reactions that develop after vaccination. A total of 332 volunteers participated in the questionnaire. Of them 247 (74.4%) were vaccinated and 85 (25.6%) were unvaccinated. Male/female ratio of the participants was 1.2, and 55.7% of them were older than 30-year-old. Most of the participants (82.8%) were highly educated (high school and faculty-graduated). Vaccination rates were found statistically significant in advanced age group compared to young adults (p= 0.042); in male gender compared to females (p= 0.001) and in parents compared to subjects who didn't have children (p= 0.021). Vaccination rates were observed to be higher (57.5%) in non-medical staff (cleaning employers, administrative personnel, etc.) than the physicians (29.1%) and nurses (13.4%), and the rate was also high (54.7%) in personnel who worked in intensive care units, emergency department and administrative units than the personnel who worked in the clinics of internal medicine (22.3%) and surgery (23.1%) (p= 0.001). The most important causes of rejecting vaccination were being afraid of the

Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

PubMed Central

Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

2015-01-01

Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192

Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals.

PubMed

Han, Kyu-Tae; Kim, Sun Jung; Lee, Seo Yoon; Park, Eun-Cheol

2014-01-01

After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Conjunctival vaccination of pregnant ewes and goats with Brucella melitensis Rev 1 vaccine: safety and serological responses.

PubMed

Zundel, E; Verger, J M; Grayon, M; Michel, R

1992-01-01

When Brucella melitensis strain Rev 1 vaccine (Rev 1) is administered by the standard method (1-2 x 10(9) viable bacteria injected subcutaneously), it may induce long-lasting serological responses and/or cause abortion in pregnant animals. The conjunctival route considerably reduces these drawbacks. In the present experiment a 1 x 10(8) CFU dose for both ewes and goats conjunctivally vaccinated at mid-pregnancy was tested for innocuousness (outcome of pregnancy, contamination of unvaccinated contact animals, duration of serological responses) in comparison with 3 x 10(8) CFU (ewes and goats), 1 x 10(9) and 3 x 10(9) CFU (ewes) doses. No reaction was observed at the time of vaccination, and the risk of environmental contamination with Rev 1, due to the conjunctival administration of the vaccine, is negligible. Abortions occurred later at surprisingly severe rates (over 60% of pregnant vaccinated animals), except in the 1 x 10(8) CFU ewes group (20%). Moreover, the serological reactions of the 1 x 10(8) CFU ewes which normally lambed were negative again as early as 12 weeks after vaccination. Although the dose of 1 x 10(8) CFU Rev 1 was safer for pregnancy than the standard dose mainly in ewes as compared to goats, the innocuousness was not yet sufficient to propose the former dose to indiscriminately vaccinate sheep and goats by the conjunctival route, whatever the age or physiological status.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

PubMed

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

PubMed

Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

2011-03-24

Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

The safety of the H1N1 influenza A vaccine in egg allergic individuals.

PubMed

Greenhawt, Matthew J; Chernin, Anna S; Howe, Laura; Li, James T; Sanders, Georgiana

2010-11-01

The safety of H1N1 vaccine is unknown in egg allergic (EA) recipients. To establish the safety of administering H1N1 vaccine and to evaluate the predictability of H1N1 skin testing in EA patients. In a controlled, prospective trial, H1N1 skin testing and vaccination was compared between EA patients (n = 105) and non-EA controls (n = 19). Those with negative H1N1 skin test results received a full H1N1 dose; those with a positive skin test result received a graded challenge (10%, 90%). Booster vaccine, if required, was given as a single dose from a different lot without prior testing. Prick and intradermal test results were positive in 3 (2.4%) of 124 and 41 (33.1%) of 124 study participants, respectively. Forty-one individuals received a 2-step graded vaccine challenge, including 13 of 25 with a history of egg anaphylaxis. No significant allergic reactions resulted from either method of vaccination or from subsequent booster doses. All study participants received the H1N1 vaccine without significant allergic reactions. Skin testing is unnecessary and does not predict vaccine tolerance. All study participants who received a graded challenge tolerated a single dose booster from a different, untested lot, including 7 individuals with a history of egg-induced anaphylaxis. We recommend administration of H1N1 vaccine to EA children without prior skin testing or graded challenge dosing. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

PubMed Central

Rao, Srinivas S.; Kong, Wing-Pui; Wei, Chih-Jen; Van Hoeven, Neal; Gorres, J. Patrick; Nason, Martha; Andersen, Hanne; Tumpey, Terrence M.; Nabel, Gary J.

2010-01-01

Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. PMID:20352112

Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial.

PubMed

Vesikari, Timo; Kirstein, Judith; Devota Go, Grace; Leav, Brett; Ruzycky, Mary Ellen; Isakov, Leah; de Bruijn, Marianne; Oberye, Janine; Heijnen, Esther

2018-05-01

Young children have immature immune systems and respond poorly to standard influenza vaccines. The oil-in-water emulsion adjuvant MF59 can increase antigen uptake, macrophage recruitment, lymph node migration, and avidity to influenza virus. Therefore, we aimed to assess the relative efficacy, immunogenicity, and safety of an MF59-adjuvanted, quadrivalent, inactivated (subunit) influenza vaccine (aIIV4) compared with a US-licensed non-adjuvanted influenza vaccine in children. We did a multicentre, randomised controlled, observer-blinded, phase 3 trial of 146 sites including hospitals, clinics, and clinician offices in nine countries over two influenza seasons. We included children of either sex aged 6 months through 5 years. We stratified eligible participants and randomly assigned them (1:1), using a block size of four, to receive either aIIV4 or non-adjuvanted inactivated influenza vaccine (ie, trivalent inactivated influenza vaccine [IIV3] or quadrivalent inactivated influenza vaccine [IIV4]). We masked participants, parents or guardians, and outcome assessors to the administered vaccine. Designated personnel who were not masked administered aIIV4 in both seasons, or IIV3 in season one and IIV4 in season two. All vaccinations were administered intramuscularly. Children aged 6 through 35 months received one or two 0·25 mL doses, whereas those aged 3 through 5 years received one or two doses of 0·5 mL. The number of doses was dependent on previous vaccination status: vaccine-naive participants received a total of two doses of study vaccine, the first on day 1 and the second on day 29, whereas non-naive participants received only one dose on day 1. The primary outcome was relative vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population and in prespecified age and dose subgroups. Immunogenicity against homologous and heterologous strains of influenza and safety were also measured. This study is registered

Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden

PubMed Central

Persson, Ingemar; Örtqvist, Åke; Bergman, Ulf; Ludvigsson, Jonas F; Granath, Fredrik

2011-01-01

Objective To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months. Design Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period. Setting Stockholm county, Sweden. Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1 024 019 were vaccinated against H1N1 and 921 005 remained unvaccinated. Main outcome measures Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell’s palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status. Results Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell’s palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

PubMed

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine.

PubMed

Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter

2012-04-01

Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.

Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

DTIC Science & Technology

1993-01-28

34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies.

PubMed

Williams, Wilton B; Liao, Hua-Xin; Moody, M Anthony; Kepler, Thomas B; Alam, S Munir; Gao, Feng; Wiehe, Kevin; Trama, Ashley M; Jones, Kathryn; Zhang, Ruijun; Song, Hongshuo; Marshall, Dawn J; Whitesides, John F; Sawatzki, Kaitlin; Hua, Axin; Liu, Pinghuang; Tay, Matthew Z; Seaton, Kelly E; Shen, Xiaoying; Foulger, Andrew; Lloyd, Krissey E; Parks, Robert; Pollara, Justin; Ferrari, Guido; Yu, Jae-Sung; Vandergrift, Nathan; Montefiori, David C; Sobieszczyk, Magdalena E; Hammer, Scott; Karuna, Shelly; Gilbert, Peter; Grove, Doug; Grunenberg, Nicole; McElrath, M Juliana; Mascola, John R; Koup, Richard A; Corey, Lawrence; Nabel, Gary J; Morgan, Cecilia; Churchyard, Gavin; Maenza, Janine; Keefer, Michael; Graham, Barney S; Baden, Lindsey R; Tomaras, Georgia D; Haynes, Barton F

2015-08-14

An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy. Copyright © 2015, American Association for the Advancement of Science.

Responses to A(H1N1)pdm09 Influenza Vaccines in Participants Previously Vaccinated With Seasonal Influenza Vaccine: A Randomized, Observer-Blind, Controlled Study

PubMed Central

Roy-Ghanta, Sumita; Van der Most, Robbert; Li, Ping; Vaughn, David W.

2014-01-01

Background. Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Methods. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4+/CD8+ T cells, memory B cells, and plasmablasts were assessed. Results. Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4+ T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4+ T cells, homologous memory B cells, and plasmablasts. Conclusions. In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed. Registration. Clinical Trials.gov identifier NCT00707967. PMID:24864125

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-01-01

In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

Cost-effectiveness of HPV vaccination regime: comparing twice versus thrice vaccinations dose regime among adolescent girls in Malaysia.

PubMed

Aljunid, Syed; Maimaiti, Namaitijiang; Nur, Amrizal M; Noor, Mohd Rushdan Md; Wan Puteh, Sharifa Ezat

2016-01-23

The HPV vaccine was introduced to Malaysian national immunization programme in 2010. The current implementation age of HPV vaccination in Malaysian is at the age of 13 years school girls, given according to a 3 doses protocol which may complicate implementation and compliance. Aim of the study is to determine the cost-effectiveness of HPV vaccination regime comparing twice versus thrice HPV vaccinations dose regime among adolescent girls in Malaysia. A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed. The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses. A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of

The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong.

PubMed

Lee, Kenneth K C; Chia Wu, David Bin; Topachevskyi, Oleksandr; Delgleize, Emmanuelle; DeAntonio, Rodrigo

2013-05-01

Pneumococcal universal vaccination in Hong Kong was introduced in 2009. We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country. An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed. Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13. Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China

PubMed Central

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670

Profiling of humoral response to influenza A(H1N1)pdm09 infection and vaccination measured by a protein microarray in persons with and without history of seasonal vaccination.

PubMed

Huijskens, Elisabeth G W; Reimerink, Johan; Mulder, Paul G H; van Beek, Janko; Meijer, Adam; de Bruin, Erwin; Friesema, Ingrid; de Jong, Menno D; Rimmelzwaan, Guus F; Peeters, Marcel F; Rossen, John W A; Koopmans, Marion

2013-01-01

The influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood. We compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination. We showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens. Seasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.

Comparative varicella vaccine effectiveness during outbreaks in day-care centres.

PubMed

Spackova, M; Wiese-Posselt, M; Dehnert, M; Matysiak-Klose, D; Heininger, U; Siedler, A

2010-01-08

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC). Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age<11 months, vaccinated at age<11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC). Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57-81, p<0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix (RR=2.8, 95%CI 1.0-7.8, p=0.05) or Priorix-Tetra (RR=2.4, 95%CI 0.7-8.3, p=0.18) but lower for 2 doses of Priorix-Tetra (RR=0.5, 95%CI 0.1-2.7, p=0.41) than for 1 dose of Varivax. Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

PubMed

Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

2016-06-08

Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of cross protection of Swine-Origin Influenza Virus (S-OIV) H1N1 and reassortant H5N1 influenza vaccine in BALB/c mice given a single-dose vaccination

PubMed Central

2013-01-01

Background Influenza virus has antigen drift and antigen shift effect, vaccination with some influenza vaccine might not induce sufficient immunity for host to the threat of other influenza virus strains. S-OIV H1N1 and H5N1 influenza vaccines in single-dose immunization were evaluated in mice for cross protection to the challenge of A/California/7/2009 H1N1 or NIBRG-14 H5N1 virus. Results Both H1N1 and H5N1 induced significant homologous IgG, HAI, and microneutralization antibody responses in the mice, while only vaccines plus adjuvant produced significant heterogeneous IgG and HAI antibody responses. Both alum and MPLA adjuvants significantly reduced the S-OIV H1N1 vaccine dose required to elicit protective HAI antibody titers from 0.05 μg to 0.001 μg. Vaccines alone did not protect mice from challenge with heterogeneous influenza virus, while H5N1 vaccine plus alum and MPLA adjuvants did. Mouse body weight loss was also less significant in the presence of adjuvant than in the vaccine without adjuvant. Furthermore, both H1N1 and H5N1 lung viral titers of immunized mice were significantly reduced post challenge with homologous viruses. Conclusion Only in the presence of MPLA adjuvant could the H5N1 vaccine significantly reduce mouse lung viral titers post H1N1 virus challenge, and not vice versa. MPLA adjuvant induced cross protection with a single dose vaccination to the challenge of heterogeneous influenza virus in mice. Lung viral titer seemed to be a better indicator compared to IgG, neutralization antibody, and HAI titer to predict survival of mice infected with influenza virus. PMID:23517052

The Swedish A(H1N1) vaccination campaign--why did not all Swedes take the vaccination?

PubMed

Björkman, Ingeborg; Sanner, Margareta A

2013-01-01

In Sweden, a mass vaccination campaign against the influenza A(H1N1) 2009 resulted in 60% vaccination coverage. However, many countries had difficulty in motivating citizens to be vaccinated. To be prepared for future vaccination campaigns, it is important to understand people's reasons for not taking the vaccination. The aim of this qualitative study was to explore motives, beliefs and reactions of individuals with varying backgrounds who did not get vaccinated. The total 28 individuals participating in the interviews were permitted to speak freely about their experiences and ideas about the vaccination. Interviews were analysed using a Grounded Theory approach. The strength of participants' decisions not to be vaccinated was also estimated. Patterns of motives were identified and described in five main categories: (A) distinguishing between unnecessary and necessary vaccination, (B) distrust, (C) the idea of the natural, (D) resisting an exaggerated safety culture, and (E) injection fear. The core category, upholding autonomy and own health, constitutes the base on which the decisions were grounded. A prerequisite for taking the vaccine would be that people feel involved in the vaccination enterprise to make a sensible decision regarding whether their health will be best protected by vaccination. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Development of an epitope-based HIV-1 vaccine strategy from HIV-1 lipopeptide to dendritic-based vaccines.

PubMed

Surenaud, Mathieu; Lacabaratz, Christine; Zurawski, Gérard; Lévy, Yves; Lelièvre, Jean-Daniel

2017-10-01

Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hépatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.

Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic

PubMed Central

Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M. Carolina; Ruiz-Matus, Cuauhtémoc

2016-01-01

ABSTRACT Background: There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. Methods: We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Results: Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6–23 months, 32% of children aged 5–2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013–14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of

Influenza vaccination in the Americas: Progress and challenges after the 2009 A(H1N1) influenza pandemic.

PubMed

Ropero-Álvarez, Alba María; El Omeiri, Nathalie; Kurtis, Hannah Jane; Danovaro-Holliday, M Carolina; Ruiz-Matus, Cuauhtémoc

2016-08-02

There has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic. We compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI). Since 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ≥60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the

Advances in HIV-1 Vaccine Development

PubMed Central

Gao, Yong

2018-01-01

An efficacious HIV-1 vaccine is regarded as the best way to halt the ongoing HIV-1 epidemic. However, despite significant efforts to develop a safe and effective vaccine, the modestly protective RV144 trial remains the only efficacy trial to provide some level of protection against HIV-1 acquisition. This review will outline the history of HIV vaccine development, novel technologies being applied to HIV vaccinology and immunogen design, as well as the studies that are ongoing to advance our understanding of vaccine-induced immune correlates of protection. PMID:29614779

H1N1 vaccination in pediatric renal transplant patients.

PubMed

Kelen, K; Ferenczi, D; Jankovics, I; Varga, M; Molnar, M Z; Sallay, P; Reusz, G; Langer, R M; Pasti, K; Gerlei, Z; Szabo, A J

2011-05-01

Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

PubMed

Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

2011-09-28

In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.

PubMed

Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne; Nyhoff, Lindsay; Harn, Donald A

2013-11-19

In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vaccination and auto-immune rheumatic diseases: lessons learnt from the 2009 H1N1 influenza virus vaccination campaign.

PubMed

Touma, Zahi; Gladman, Dafna D; Urowitz, Murray B

2013-03-01

To determine the safety and efficacy of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. Due to immune abnormalities and the use of steroids and immunosuppressant treatment, patients with rheumatic diseases are susceptible to infections including influenza. Infections continue to be one of the leading causes of morbidity and mortality in rheumatic diseases, partly due to the disease processes and partly due to medications. Viral infections are particularly an issue, so vaccinations would be advisable. However, because of the abnormalities in immune mechanisms in many rheumatic diseases, it is not clear whether vaccinations are well tolerated and effective. A number of studies confirmed the efficacy and safety of adjuvant and nonadjuvant influenza A/H1NI vaccination in patients with rheumatic diseases. The potential side effects associated with H1N1 vaccines were not different from those observed with seasonal influenza vaccine. The use of steroids and immunosuppressant therapies may alter the efficacy of the vaccines. Adjuvant and nonadjuvant influenza A/H1NI vaccinations have no clinically important effect on production or levels of autoantibodies in patients with rheumatic diseases. H1N1 vaccination should be given to patients with rheumatic diseases.

[H1N1 influenza vaccines in Tunisia: efficiency and safety].

PubMed

Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Toumi, Adnen; Braham, Dorra; A Boughattas, Naceur; Chakroun, Mohamed

2011-01-01

We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(®) and Panenza(®). It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. method. The number of subjects vaccinated by Focetria(®) is more important than Panenza(®). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(®) adverse effects were more frequent than Panenza(®) ones (p = 0.009). Almost all adverse events disappeared within few days. The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. © 2011 Société Française de Pharmacologie et de Thérapeutique.

Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy).

PubMed

Amodio, Emanuele; Anastasi, Giovanna; Marsala, Maria Grazia Laura; Torregrossa, Maria Valeria; Romano, Nino; Firenze, Alberto

2011-02-04

The aim of the study was to investigate factors involved in vaccination acceptance among healthcare workers (HCWs) and adverse reactions rates associated with pandemic influenza vaccination. The study was carried out in the major teaching hospital of Sicily from November 2009 to February 2010 on 2267 HCWs. A total of 407 (18%) HCWs were vaccinated against the 2009 pandemic influenza A (H1N1). A logistic regression analysis indicates an increased risk of non-vaccination against pandemic influenza in females (OR=1.6; 95% CI=1.3-2.1) compared to males, in nurses/technicians/administrative workers (OR=1.7; 95% CI=1.3-2.2) compared to doctors/biologists, and in HCWs who were non-vaccinated against seasonal influenza in 2008-2009 (OR=4.9; 95% CI=3.7-6.5) compared to vaccinated HCWs. Overall, 302 (74.2%) out of 407 questionnaires distributed to vaccinated HCWs were returned within the observation period. One hundred fifty-two workers (50.3%) experienced at least one adverse reaction (30.1%, local reactions; 6.6% systemic reactions and 13.6% both of them). The most frequent side effect of vaccination was pain at the injection site (43.4%). Twelve (3.9%) out of 302 HCWs stated they experienced influenza-like illness episodes during the follow-up period. The use of an adjuvanted vaccine against pandemic influenza A (H1N1) appears to be an effective and safe preventive strategy, showing a prevalence of both local and systemic adverse reactions not very different from that seen after vaccination with non-adjuvanted seasonal influenza vaccine. Despite this finding, vaccination coverage among HCWs remains very low, suggesting the need to implement educational campaigns directed to groups with lower coverage rates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lessons from HIV-1 vaccine efficacy trials.

PubMed

Excler, Jean-Louis; Michael, Nelson L

2016-11-01

Only four HIV-1 vaccine concepts have been tested in six efficacy trials with no product licensed to date. Several scientific and programmatic lessons can be learned from these studies generating new hypotheses and guiding future steps. RV144 [ALVAC-HIV (canarypox vector) and AIDSVAX B/E (bivalent gp120 HIV-1 subtype B and CRF01_AE)] remains the only efficacy trial that demonstrated a modest vaccine efficacy, which led to the identification of immune correlates of risk. Progress on subtype-specific, ALVAC (canarypox vector) and gp120 vaccine prime-boost approaches has been slow, but we are finally close to the launch of an efficacy study in Africa in 2016. The quest of a globally effective HIV-1 vaccine has led to the development of new approaches. Efficacy studies of combinations of Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 vaccines with mosaic designs will enter efficacy studies mid-2017 and cytomegalovirus (CMV)-vectored vaccines begin Phase I studies at the same time. Future HIV-1 vaccine efficacy trials face practical challenges as effective nonvaccine prevention programs are projected to decrease HIV-1 incidence. An HIV-1 vaccine is urgently needed. Increased industry involvement, mobilization of resources, expansion of a robust pipeline of new concepts, and robust preclinical challenge studies will be essential to accelerate efficacy testing of next generation HIV-1 vaccine candidates.

Comparing live attenuated and inactivated hepatitis A vaccines: an immunogenicity study after one single dose.

PubMed

Zheng, Hui; Chen, Yuansheng; Wang, Fuzhen; Gong, Xiaohong; Wu, Zhenhua; Miao, Ning; Zhang, Xiaoshu; Li, Hui; Chen, Chao; Hou, Xiang; Cui, Fuqiang; Wang, Huaqing

2011-11-08

While three types of hepatitis A vaccines are available in China, little data are available to compare them in terms of early antibody response. We conducted a trial to compare antibody response at 7, 14 and 28 days. We randomized primary school children in Gansu and Jilin provinces into four groups to receive either (1) Chinese live attenuated hepatitis A vaccine (H2 strain), (2) domestic inactivated hepatitis A vaccine (Healive(®)), (3) imported inactivated hepatitis A vaccine (Havrix(®)) or (4) hepatitis B vaccine (Control group). We compared groups at 7, 14 and 28 days in terms of proportion of sero-conversions (≥10 mUI/ml), and Geometric Mean Concentration (GMC) of antibodies measured with a Microparticle Enzyme Immunoassay (MEIA). We compared rates of self-reported adverse events following immunization (AEFI) in the first three days. 204 children received the H2 vaccine, 208 received Healive(®), 214 received Havrix(®), and 215 received hepatitis B vaccine (no differences across groups in terms of age, sex, weight and height). At seven days, sero-conversion proportions were 25%, 35%, 27% and 2% (p<0.0001) with GMC of 6 mIU/ml, 8 mIU/ml, 6 mIU/ml and 3 mIU/ml, respectively for the four groups. At 28 days, sero-conversion proportions were 98%, 100%, 93% and 3% (p<0.0001) with GMC of 47 mIU/ml, 71 mIU/ml, 67 mIU/ml and 3 mIU/ml, respectively. AEFI were benign and did not differ across groups (p=0.94). While our study was not able to identify differences between Havrix(®), Healive(®) and H2 vaccine in terms of sero-conversion proportion and GMC between seven and 28 days, further studies should evaluate non-inferiority or equivalence of the Chinese vaccines, particularly with respect to the GMC concentration for the H2 vaccine since it could affect long-term protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

AIDS vaccines that allow HIV-1 to infect and escape immunologic control: a mathematic analysis of mass vaccination.

PubMed

van Ballegooijen, Marijn; Bogaards, Johannes A; Weverling, Gerrit-Jan; Boerlijst, Maarten C; Goudsmit, Jaap

2003-10-01

Cytotoxic T lymphocyte (CTL)-based HIV vaccine concepts shown to reduce viremia and postpone disease but not to prevent infection in monkeys are currently in human phase 1 trials. To evaluate the potential efficacy of vaccines that cannot prevent HIV-1 to infect and escape immunologic control, we designed a mathematic model that correlates the level of viremia to both infectiousness and disease progression. We speculate that vaccinees will have a virologic set point and disease progression rates comparable to untreated HIV-1-infected individuals with the best prognosis. Our model (illustrated with R0 = 3) shows that a sexually active population can ultimately be reduced to 26% of its initial size as a result of AIDS-related mortality in the absence of treatment or vaccination. Start of vaccination when HIV-1 prevalence is still low might postpone the peak incidence of infection and the dramatic decline in population size by up to 22 years. In conclusion, CTL-based vaccines that do not prevent HIV-1 infection but do postpone the time to onset of AIDS have considerable potential to curb the spread of HIV-1 and to postpone high AIDS-related mortality on a population level. The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however.

Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

PubMed Central

He, Xiao-Song; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

2013-01-01

Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. PMID:23107783

Partners in immunization: 2010 survey examining differences among H1N1 vaccine providers in Washington state.

PubMed

Seib, Katherine; Gleason, Cindy; Richards, Jennifer L; Chamberlain, Allison; Andrews, Tracey; Watson, Lin; Whitney, Ellen; Hinman, Alan R; Omer, Saad B

2013-01-01

Emergency response involving mass vaccination requires the involvement of traditional vaccine providers as well as other health-care providers, including pharmacists, obstetricians, and health-care providers at correctional facilities. We explored differences in provider experiences administering pandemic vaccine during a public health emergency. We conducted a cross-sectional survey of H1N1 vaccine providers in Washington State, examining topics regarding pandemic vaccine administration, participation in preparedness activities, and communication with public health agencies. We also examined differences among provider types in responses received (n=619, 80.9% response rate). Compared with other types of vaccine providers (e.g., family practitioners, obstetricians, and specialists), pharmacists reported higher patient volumes as well as higher patient-to-practitioner ratios, indicating a broad capacity for community reach. Pharmacists and correctional health-care providers reported lower staff coverage with seasonal and H1N1 vaccines. Compared with other vaccine providers, pharmacists were also more likely to report relying on public health information from federal sources. They were less likely to report relying on local health departments (LHDs) for pandemic-related information, but indicated a desire to be included in LHD communications and plans. While all provider types indicated a high willingness to respond to a public health emergency, pharmacists were less likely to have participated in training, actual emergency response, or surge capacity initiatives. No obstetricians reported participating in surge capacity initiatives. Results from this survey suggest that efforts to increase communication and interaction between public health agencies and pharmacy, obstetric, and correctional health-care vaccine providers may improve future preparedness and emergency response capability and reach.

Partners in Immunization: 2010 Survey Examining Differences Among H1N1 Vaccine Providers in Washington State

PubMed Central

Gleason, Cindy; Richards, Jennifer L.; Chamberlain, Allison; Andrews, Tracey; Watson, Lin; Whitney, Ellen; Hinman, Alan R.; Omer, Saad B.

2013-01-01

Objectives Emergency response involving mass vaccination requires the involvement of traditional vaccine providers as well as other health-care providers, including pharmacists, obstetricians, and health-care providers at correctional facilities. We explored differences in provider experiences administering pandemic vaccine during a public health emergency. Methods We conducted a cross-sectional survey of H1N1 vaccine providers in Washington State, examining topics regarding pandemic vaccine administration, participation in preparedness activities, and communication with public health agencies. We also examined differences among provider types in responses received (n=619, 80.9% response rate). Results Compared with other types of vaccine providers (e.g., family practitioners, obstetricians, and specialists), pharmacists reported higher patient volumes as well as higher patient-to-practitioner ratios, indicating a broad capacity for community reach. Pharmacists and correctional health-care providers reported lower staff coverage with seasonal and H1N1 vaccines. Compared with other vaccine providers, pharmacists were also more likely to report relying on public health information from federal sources. They were less likely to report relying on local health departments (LHDs) for pandemic-related information, but indicated a desire to be included in LHD communications and plans. While all provider types indicated a high willingness to respond to a public health emergency, pharmacists were less likely to have participated in training, actual emergency response, or surge capacity initiatives. No obstetricians reported participating in surge capacity initiatives. Conclusions Results from this survey suggest that efforts to increase communication and interaction between public health agencies and pharmacy, obstetric, and correctional health-care vaccine providers may improve future preparedness and emergency response capability and reach. PMID:23633735

Impact of Body Mass Index on Immunogenicity of Pandemic H1N1 Vaccine in Children and Adults

PubMed Central

Callahan, S. Todd; Wolff, Mark; Hill, Heather R.; Edwards, Kathryn M.; Keitel, Wendy; Atmar, Robert; Patel, Shital; Sahly, Hana El; Munoz, Flor; Paul Glezen, W.; Brady, Rebecca; Frenck, Robert; Bernstein, David; Harrison, Christopher; Jackson, Mary Anne; Swanson, Douglas; Newland, Jason; Myers, Angela; Livingston, Robyn A; Walter, Emmanuel; Dolor, Rowena; Schmader, Kenneth; Mulligan, Mark J.; Edupuganti, Srilatha; Rouphael, Nadine; Whitaker, Jennifer; Spearman, Paul; Keyserling, Harry; Shane, Andi; Eckard, Allison Ross; Jackson, Lisa A.; Frey, Sharon E.; Belshe, Robert B.; Graham, Irene; Anderson, Edwin; Englund, Janet A.; Healy, Sara; Winokur, Patricia; Stapleton, Jack; Meier, Jeffrey; Kotloff, Karen; Chen, Wilbur; Hutter, Julia; Stephens, Ina; Wooten, Susan; Wald, Anna; Johnston, Christine; Edwards, Kathryn M.; Buddy Creech, C.; Todd Callahan, S.

2014-01-01

Obesity emerged as a risk factor for morbidity and mortality related to 2009 pandemic influenza A (H1N1) infection. However, few studies examine the immune responses to H1N1 vaccine among children and adults of various body mass indices (BMI). Pooling data from 3 trials of unadjuvanted split-virus H1N1 A/California/07/2009 influenza vaccines, we analyzed serologic responses of participants stratified by BMI grouping. A single vaccine dose produced higher hemagglutination inhibition antibody titers at day 21 in obese compared to nonobese adults, but there were no significant differences in responses to H1N1 vaccine among children or adults of various BMI following 2 doses. PMID:24795475

Evaluation of humoral and cellular immune responses against HSV-1 using genetic immunization by filamentous phage particles: a comparative approach to conventional DNA vaccine.

PubMed

Hashemi, Hamidreza; Bamdad, Taravat; Jamali, Abbas; Pouyanfard, Somayeh; Mohammadi, Masoumeh Gorgian

2010-02-01

Phage display is based on expressing peptides as a fusion to one of the phage coat proteins. To date, many vaccine researches have been conducted to display immunogenic peptides or mimotopes of various pathogens and tumors on the surface of filamentous bacteriophages. In recent years as a new approach to application of phages, recombinant bacteriophage lambda particles were used as DNA delivery vehicles to mammalian cells. In this study, recombinant filamentous phage whole particles were used for vaccination of mice. BALB/c mice were inoculated with filamentous phage particles containing expression cassette of Herpes simplex virus 1 (HSV-1) glycoprotein D that has essential roles in the virus attachment and entry. Both humoral and cellular immune responses were measured in the immunized mice and compared to conventional DNA vaccination. A dose-response relationship was observed in both arms of immune responses induced by recombinant filamentous phage inoculation. The results were similar to those from DNA vaccination. Filamentous phages can be considered as suitable alternative candidate vaccines because of easier and more cost-effective production and purification over plasmid DNA or bacteriophage lambda particles. 2009 Elsevier B.V. All rights reserved.

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

PubMed Central

Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew

2015-01-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

Immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: A phase 3, randomized noninferiority study.

PubMed

Airey, Jolanta; Albano, Frank R; Sawlwin, Daphne C; Jones, Alison Graves; Formica, Neil; Matassa, Vince; Leong, Jane

2017-05-09

Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5-17years. Participants (N=2278) were randomized 3:1 and stratified by age (5-8years; 9-17years) to receive IIV4 (n=1709) or comparator IIV4 (n=569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI]≤1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI≤10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively. IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were -3.1 (-8.0, 1.8), 0.4 (-4.5, 5.3), -3.4 (-8.3, 1.5), and -2.0 (-6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported. IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5-17years. Increased levels of virus splitting agent seem to

Comparative cost effectiveness of varicella, hepatitis A, and pneumococcal conjugate vaccines.

PubMed

Jacobs, R J; Meyerhoff, A S

2001-12-01

Several state and local U.S. governments are considering making varicella, hepatitis A, and/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is confounded by their dissimilar methods. We reviewed U.S. cost-effectiveness studies of childhood varicella, hepatitis A, and pneumococcal conjugate vaccines and identified four providing data required to standardize methods. Vaccination, disease treatment, and work-loss costs were estimated from original study results and current prices. Estimated life-years saved were derived from original study results, epidemiological evidence, and alternative procedures for discounting to present values. Hepatitis A vaccine would have the lowest health system costs per life-year saved. Varicella vaccine would provide the greatest reduction in societal costs, mainly through reduced parent work loss. Pneumococcal conjugate vaccine would cost twice the amount of varicella and hepatitis A vaccines combined and be less cost effective than the other vaccines. Hepatitis A and varicella vaccines, but not pneumococcal conjugate vaccine, meet or exceed conventional standards of cost effectiveness. Copyright 2001 American Health Foundation and Elsevier Science.

H1N1 antibody persistence 1 year after immunization with an adjuvanted or whole-virion pandemic vaccine and immunogenicity and reactogenicity of subsequent seasonal influenza vaccine: a multicenter follow-on study.

PubMed

Walker, Woolf T; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T; Miller, Elizabeth; Faust, Saul N; Snape, Matthew D; Finn, Adam; Pollard, Andrew J

2012-03-01

We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

PubMed Central

Walker, Woolf T.; de Whalley, Philip; Andrews, Nick; Oeser, Clarissa; Casey, Michelle; Michaelis, Louise; Hoschler, Katja; Harrill, Caroline; Moulsdale, Phoebe; Thompson, Ben; Jones, Claire; Chalk, Jem; Kerridge, Simon; John, Tessa M.; Okike, Ifeanyichukwu; Ladhani, Shamez; Tomlinson, Richard; Heath, Paul T.; Miller, Elizabeth; Snape, Matthew D.; Finn, Adam; Pollard, Andrew J.

2012-01-01

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain. PMID:22267719

Guillain-Barré Syndrome During the 2009–2010 H1N1 Influenza Vaccination Campaign: Population-based Surveillance Among 45 Million Americans

PubMed Central

Wise, Matthew E.; Viray, Melissa; Sejvar, James J.; Lewis, Paige; Baughman, Andrew L.; Connor, Walter; Danila, Richard; Giambrone, Greg P.; Hale, Christa; Hogan, Brenna C.; Meek, James I.; Murphree, Rendi; Oh, John Y.; Reingold, Arthur; Tellman, Norisse; Conner, Susan M.; Singleton, James A.; Lu, Peng-Jun; DeStefano, Frank; Fridkin, Scott K.; Vellozzi, Claudia; Morgan, Oliver W.

2012-01-01

Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barré syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009–May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments. PMID:22582209

Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012-2013.

PubMed

Payne, Daniel C; Selvarangan, Rangaraj; Azimi, Parvin H; Boom, Julie A; Englund, Janet A; Staat, Mary Allen; Halasa, Natasha B; Weinberg, Geoffrey A; Szilagyi, Peter G; Chappell, James; McNeal, Monica; Klein, Eileen J; Sahni, Leila C; Johnston, Samantha H; Harrison, Christopher J; Baker, Carol J; Bernstein, David I; Moffatt, Mary E; Tate, Jacqueline E; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Wikswo, Mary E; Curns, Aaron T; Sulemana, Iddrisu; Bowen, Michael D; Gentsch, Jon R; Parashar, Umesh D

2015-12-15

Using a multicenter, active surveillance network from 2 rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata. We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the vaccine effectiveness (VE) for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity. RV5-specific VE analyses included 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [CI], 74%-84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI, 68%-88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains. In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting and broadly heterologous protection against rotavirus gastroenteritis. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in

Effect of Abatacept on Immunogenicity of Vaccines in Individuals with Type 1 Diabetes

PubMed Central

Weinberg, Adriana; Boulware, David; Dighero, Bonnie; Orban, Tihamer

2013-01-01

Abatacept delayed progression of type 1 diabetes (T1D) when administered soon after diagnosis. Its use in T1D is expanding to prevention trials and, therefore, it is important to fully characterize its immunosuppressive effect. We compared antibody responses to trivalent inactivated influenza vaccine (TIIV) administered during 2 consecutive seasons and to tetanus toxoid (TT) vaccine administered after 24 months of treatment in115 early onset T1D subjects randomly assigned to 24 months of Abatacept (N=71) or placebo (N=34). Anti-influenza titers before TIIV were similar between the 2 treatment groups and both groups had significant increases after vaccination. Although the magnitude of antibody responses against some influenza serotypes was significantly lower (p<0.05) in Abatacept compared with placebo recipients, no differences were observed in the proportion of subjects with protective titers against influenza after vaccination. The magnitude of antibody responses against TT also tended to be lower (p=0.06) in Abatacept compared with placebo recipients, without affecting the proportion of subjects who achieved protective titers. We conclude that Abatacept moderately decreases the magnitude of antibody responses to recall vaccination. Further studies are needed to assess its effect on primary immunization. PMID:23962535

Effect of abatacept on immunogenicity of vaccines in individuals with type 1 diabetes.

PubMed

Weinberg, Adriana; Boulware, David; Dighero, Bonnie; Orban, Tihamer

2013-10-01

Abatacept delayed progression of type 1 diabetes (T1D) when administered soon after diagnosis. Its use in T1D is expanding to prevention trials and, therefore, it is important to fully characterize its immunosuppressive effect. We compared antibody responses to trivalent inactivated influenza vaccine (TIIV) administered during 2 consecutive seasons and to tetanus toxoid (TT) vaccine administered after 24 months of treatment in115 early onset T1D subjects randomly assigned to 24 months of abatacept (N=71) or placebo (N=34). Anti-influenza titers before TIIV were similar between the 2 treatment groups and both groups had significant increases after vaccination. Although the magnitude of antibody responses against some influenza serotypes was significantly lower (p<0.05) in abatacept compared with placebo recipients, no differences were observed in the proportion of subjects with protective titers against influenza after vaccination. The magnitude of antibody responses against TT also tended to be lower (p=0.06) in abatacept compared with placebo recipients, without affecting the proportion of subjects who achieved protective titers. We conclude that abatacept moderately decreases the magnitude of antibody responses to recall vaccination. Further studies are needed to assess its effect on primary immunization. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.

PubMed

Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai

2017-06-03

The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without

Effective Protection Induced by a Monovalent DNA Vaccine against Dengue Virus (DV) Serotype 1 and a Bivalent DNA Vaccine against DV1 and DV2 in Mice.

PubMed

Zheng, Xiaoyan; Chen, Hui; Wang, Ran; Fan, Dongying; Feng, Kaihao; Gao, Na; An, Jing

2017-01-01

Dengue virus (DV) is the causal pathogen of dengue fever, which is one of the most rapidly spread mosquito-borne disease worldwide and has become a severe public health problem. Currently, there is no specific treatment for dengue; thus, a vaccine would be an effective countermeasure to reduce the morbidity and mortality. Although, the chimeric Yellow fever dengue tetravalent vaccine has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate pVAX1-D1ME expressing the prME protein of DV1 was inoculated in BALB/c mice via intramuscular injection or electroporation, and the immunogenicity and protection were evaluated. Compared with traditional intramuscular injection, administration with 50 μg pVAX1-D1ME via electroporation with three immunizations induced persistent humoral and cellular immune responses and effectively protected mice against lethal DV1 challenge. In addition, immunization with a bivalent vaccine consisting of pVAX1-D1ME and pVAX1-D2ME via electroporation generated a balanced IgG response and neutralizing antibodies against DV1 and DV2 and could protect mice from lethal challenge with DV1 and DV2. This study sheds new light on developing a dengue tetravalent DNA vaccine.

Protective immune response of chickens to oral vaccination with thermostable live Fowlpox virus vaccine (strain TPV-1) coated on oiled rice.

PubMed

Wambura, Philemon N; Godfrey, S K

2010-03-01

The objective of the present study was to develop and evaluate a local vaccine (strain TPV-1) against Fowl pox (FP) in chickens. Two separate groups of chickens were vaccinated with FP vaccine through oral (coated on oiled rice) and wing web stab routes, respectively. The results showed that the haemagglutination-inhibition (HI) antibody titres in both vaccinated groups were comparable and significantly higher (P < 0.05) than the control chickens. It was further revealed that 14 days after vaccination HI GMT of > or =2 log(2) was recorded in chickens vaccinated by oral and wing web stab routes whereas 35 days after vaccination the HI antibody titres reached 5.6 log(2) and 6.3 log(2), respectively. Moreover, in both groups the birds showed 100% protection against challenge virus at 35 days after vaccination. The findings from the present study have shown that oral route is equally effective as wing web stab route for vaccination of chickens against FP. However, the oral route can be used in mass vaccination of birds thus avoid catching individual birds for vaccination. It was noteworthy that strain TPV-1 virus could be propagated by a simple allantoic cavity inoculation and harvesting of allantoic fluid where it survived exposure at 57 degrees C for 2 hours. If the oral vaccination technique is optimized it may be used in controlling FP in scavenging and feral chickens. In conclusion, the present study has shown that FP vaccine (strain TPV-1) was safe, thermostable, immunogenic and efficacious in vaccinated chickens.

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine.

PubMed

McGuire, Erin P; Fong, Youyi; Toote, Christopher; Cunningham, Coleen K; McFarland, Elizabeth J; Borkowsky, William; Barnett, Susan; Itell, Hannah L; Kumar, Amit; Gray, Glenda; McElrath, M Julianna; Tomaras, Georgia D; Permar, Sallie R; Fouda, Genevieve G

2018-01-01

In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59- and alum-adjuvanted HIV envelope vaccines. At peak immunogenicity, the magnitudes of the gp120- and V1V2-specific IgG responses were comparable between adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510, P = 0.070; V1V2 median MFIs of 512 [infants] and 804 [adults], P = 0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults], P < 0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults]; P < 0.001). Six months after peak immunogenicity, infants maintained higher levels Env-specific IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120-vaccinated infants but only in 12% of the vaccinated adults ( P = 0.0018). Finally, in contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine-elicited Env-specific IgA was frequently detected in adults. Our results suggest that vaccine adjuvants differently modulate gp120-specific antibody responses in adults and infants and that infants can robustly respond to HIV Env immunization. IMPORTANCE More than 150,000 pediatric HIV infections occur yearly, despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine could

Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.

PubMed

Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

2017-04-06

Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

PubMed

Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

2015-04-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Influenza Virus Vaccines: Lessons from the 2009 H1N1 pandemic

PubMed Central

Broadbent, Andrew J.; Subbarao, Kanta

2011-01-01

Reflecting on the 2009 H1N1 pandemic, we summarize lessons regarding influenza vaccines that can be applied in the future. The two major challenges to vaccination during the 2009 H1N1 pandemic were timing and availability of vaccine. Vaccines were, however, well-tolerated and immunogenic, with inactivated vaccines containing 15μg of HA generally inducing antibody titers ≥1:40 in adults within 2 weeks of the administration of a single dose. Moreover, the use of oil-in-water adjuvants in Europe permitted dose- reduction, with vaccines containing as little as 3.75 or 7.5μg HA being immunogenic. Case-control studies demonstrated that monovalent 2009 H1N1 vaccines were effective in preventing infection with the 2009 H1N1 virus, but preliminary data suggests that it is important for individuals to be re-immunized annually. PMID:22125588

The Effects of Capillary Transit Time Heterogeneity (CTH) on the Cerebral Uptake of Glucose and Glucose Analogs: Application to FDG and Comparison to Oxygen Uptake

PubMed Central

Angleys, Hugo; Jespersen, Sune N.; Østergaard, Leif

2016-01-01

Glucose is the brain's principal source of ATP, but the extent to which cerebral glucose consumption (CMRglc) is coupled with its oxygen consumption (CMRO2) remains unclear. Measurements of the brain's oxygen-glucose index OGI = CMRO2/CMRglc suggest that its oxygen uptake largely suffices for oxidative phosphorylation. Nevertheless, during functional activation and in some disease states, brain tissue seemingly produces lactate although cerebral blood flow (CBF) delivers sufficient oxygen, so-called aerobic glycolysis. OGI measurements, in turn, are method-dependent in that estimates based on glucose analog uptake depend on the so-called lumped constant (LC) to arrive at CMRglc. Capillary transit time heterogeneity (CTH), which is believed to change during functional activation and in some disease states, affects the extraction efficacy of oxygen from blood. We developed a three-compartment model of glucose extraction to examine whether CTH also affects glucose extraction into brain tissue. We then combined this model with our previous model of oxygen extraction to examine whether differential glucose and oxygen extraction might favor non-oxidative glucose metabolism under certain conditions. Our model predicts that glucose uptake is largely unaffected by changes in its plasma concentration, while changes in CBF and CTH affect glucose and oxygen uptake to different extents. Accordingly, functional hyperemia facilitates glucose uptake more than oxygen uptake, favoring aerobic glycolysis during enhanced energy demands. Applying our model to glucose analogs, we observe that LC depends on physiological state, with a risk of overestimating relative increases in CMRglc during functional activation by as much as 50%. PMID:27790110

Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1.

PubMed

Amer, Ahdi; Fischer, Howard; Li, Xiaoming; Asmar, Basim

2016-03-01

Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. This was a retrospective case-control study. We reviewed the medical records of polymerase chain reaction-confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. © The Author(s) 2015.

A comparative analysis of the epidemiological impact and disease cost-savings of HPV vaccines in France.

PubMed

Bresse, Xavier; Adam, Marjorie; Largeron, Nathalie; Roze, Stephane; Marty, Rémi

2013-04-01

The aim was to compare the epidemiological and economic impact of 16/18 bivalent and 6/11/16/18 quadrivalent HPV vaccination in France, considering differences in licensed outcomes, protection against non-vaccine HPV types and prevention of HPV-6/11-related diseases. The differential impact of the two vaccines was evaluated using a published model adapted to the French setting. The target population was females aged 14-23 y and the time horizon was 100 y. A total of eight different scenarios compared vaccination impact in terms of reduction in HPV-16/18-associated carcinomas (cervical, vulvar, vaginal, anal, penile and head and neck), HPV-6/11-related genital warts and recurrent respiratory papillomatosis, and incremental reduction in cervical cancer due to potential cross-protection. Quadrivalent vaccine was associated with total discounted cost savings ranging from EUR 544-1,020 million vs. EUR 177-538 million with the bivalent vaccination (100-y time horizon). Genital wart prevention thanks to quadrivalent HPV vaccination accounted for EUR 306-380 million savings (37-56% of costs saved). In contrast, the maximal assumed cross-protection against cervical cancer resulted in EUR 13-33 million savings (4%). Prevention of vulvar, vaginal and anal cancers accounted for additional EUR 71-89 million savings (13%). In France, the quadrivalent HPV vaccination would result in significant incremental epidemiological and economic benefits vs. the bivalent vaccination, driven primarily by prevention of genital. The present analysis is the first in the French setting to consider the impact of HPV vaccination on all HPV diseases and non-vaccine types.

Protective effect of A/H1N1 vaccination in immune-mediated disease--a prospectively controlled vaccination study.

PubMed

Adler, Sabine; Krivine, Anne; Weix, Janine; Rozenberg, Flore; Launay, Odile; Huesler, Juerg; Guillevin, Loïc; Villiger, Peter M

2012-04-01

To assess the 2009 influenza vaccine A/H1N1 on antibody response, side effects and disease activity in patients with immune-mediated diseases. Patients with RA, SpA, vasculitis (VAS) or CTD (n = 149) and healthy individuals (n = 40) received a single dose of adjuvanted A/H1N1 influenza vaccine. Sera were obtained before vaccination, and 3 weeks, 6 weeks and 6 months thereafter. A/H1N1 antibody titres were measured by haemagglutination inhibition (HAI) assay. Seroprotection was defined as specific antibody titre ≥ 1 : 40, seroconversion as 4-fold increase in antibody titre. Titres increased significantly in patients and controls with a maximum at Week 3, declining to levels below protection at Month 6 (P < 0.001). Seroprotection was more frequently reached in SpA and CTD than in RA and VAS (80 and 82% and 57 and 47%, respectively). There was a significantly negative impact by MTX (P < 0.001), rituximab (P = 0.0031) and abatacept (P = 0.045). Other DMARDs, glucocorticoids and TNF blockers did not significantly suppress response (P = 0.06, 0.11 and 0.81, respectively). A linear decline in response was noted in patients with increasing age (P < 0.001). Disease reactivation possibly related to vaccination was suspected in 8/149 patients. No prolonged side effects or A/H1N1 infections were noted. The results show that vaccination response is a function of disease type, intensity and character of medication and age. A single injection of adjuvanted influenza vaccine is sufficient to protect a high percentage of patients. Therefore, differential vaccination recommendations might in the future reduce costs and increase vaccination acceptance.

Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009-2010.

PubMed

Eaton, Abigail; Lewis, Ned; Fireman, Bruce; Hansen, John; Baxter, Roger; Gee, Julianne; Klein, Nicola P

2018-05-03

Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

PubMed

Greenberg, David P; Robertson, Corwin A; Noss, Michael J; Blatter, Mark M; Biedenbender, Rex; Decker, Michael D

2013-01-21

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

PubMed Central

Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Diallo, Dapa A.; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Dicko, Alassane; Sagara, Issaka; Sissoko, Mahamadou S.; Baby, Mounirou; Sissoko, Mady; Diarra, Issa; Niangaly, Amadou; Dolo, Amagana; Daou, Modibo; Diawara, Sory I.; Heppner, D. Gray; Stewart, V. Ann; Angov, Evelina; Bergmann-Leitner, Elke S.; Lanar, David E.; Dutta, Sheetij; Soisson, Lorraine; Diggs, Carter L.; Leach, Amanda; Owusu, Alex; Dubois, Marie-Claude; Cohen, Joe; Nixon, Jason N.; Gregson, Aric; Takala, Shannon L.; Lyke, Kirsten E.; Plowe, Christopher V.

2008-01-01

Background The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site. Trial Registration ClinicalTrials.gov NCT00308061 PMID:18213374

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial

PubMed Central

Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai

2017-01-01

ABSTRACT Background: The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. Methods: A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4–6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Results: Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = −2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: −6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: −1.50%, 8.48%) between I-B-B and I-T-T and −2.32% (95% CI: −5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of −10%. Of 24 serious adverse events reported, no one was vaccine-related. Conclusions: The vaccination schedules with bOPV followed by one or 2 doses of IPV were

Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009 A/H1N1 Influenza Vaccination.

PubMed

Fell, Deshayne B; Wilson, Kumanan; Ducharme, Robin; Hawken, Steven; Sprague, Ann E; Kwong, Jeffrey C; Smith, Graeme; Wen, Shi Wu; Walker, Mark C

2016-01-01

Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia. We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores. Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27-3.76 and 3.60, 95% CI: 2.51-5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period. We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited.

Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines.

PubMed

Couch, Robert B; Atmar, Robert L; Keitel, Wendy A; Quarles, John M; Wells, Janet; Arden, Nancy; Niño, Diane

2012-12-17

and frequencies were low for the N1 of A/H1N1 virus. Trivalent inactivated influenza vaccines with similar HA dosage induce similar serum anti-HA antibody responses in healthy adults. Current inactivated vaccines all induce serum anti-NA antibody to the N1 and N2 NA proteins but some are better than others for N1 or N2. The live vaccine, Flumist, was a poor inducer of either anti-HA or anti-NA serum antibody compared to inactivated vaccine in the healthy adults. In view of the capacity for contributing to immunity to influenza in humans, developing guidelines for NA content and induction of NA antibody is desirable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Serologic response to porcine circovirus type 1 (PCV1) in infants vaccinated with the human rotavirus vaccine, Rotarix™: A retrospective laboratory analysis

PubMed Central

Han, Htay Htay; Karkada, Naveen; Jayadeva, Girish; Dubin, Gary

2017-01-01

ABSTRACT In 2010, porcine circovirus type 1 (PCV1) material was unexpectedly detected in the oral live-attenuated human rotavirus (RV) vaccine, Rotarix™ (GSK Vaccines, Belgium). An initial study (NCT01511133) found no immunologic response against PCV1 in 40 vaccinated infants. As a follow-up, the current study (NCT02153333), searched for evidence of post-vaccination serologic response to PCV1 in a larger number of archived serum samples. Unlike the previous study, serum anti-PCV1 antibodies were assessed with an adapted Immuno Peroxidase Monolayer Assay (IPMA) using a Vero-adapted PCV1 strain. Samples from 596 infants who participated in clinical trials of the human RV vaccine were randomly selected and analyzed. The observed anti-PCV1 antibody seropositivity rate 1–2 months post-dose 2 was approximately 1% [90% Confidence Interval (CI): 0.3–2.6] (3/299 samples) in infants who received the human RV vaccine and 0.3% [90% CI: 0.0–1.6] (1/297 samples) in those who received placebo; the difference between the groups was −0.66 [90% CI: −2.16–0.60]. One subject in the vaccinated group was also seropositive before vaccination. Notably, the seropositivity rate observed in vaccinated subjects was below that observed during assay qualification in samples from unvaccinated subjects outside of this study (2.5%; 5/200 samples). No serious adverse events had been reported in any of the 4 subjects providing anti-PCV1 positive samples during the 31-day post-vaccination follow-up period in the original studies. In conclusion, the presence of PCV1 in the human RV vaccine is considered to be a manufacturing quality issue and does not appear to pose a safety risk to vaccinated infants. PMID:27657348

Suboptimal protection against H5N1 highly pathogenic avian influenza viruses from Vietnam in ducks vaccinated with commercial poultry vaccines.

PubMed

Cha, Ra Mi; Smith, Diane; Shepherd, Eric; Davis, C Todd; Donis, Ruben; Nguyen, Tung; Nguyen, Hoang Dang; Do, Hoa Thi; Inui, Ken; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary

2013-10-09

Domestic ducks are the second most abundant poultry species in many Asian countries including Vietnam, and play a critical role in the epizootiology of H5N1 highly pathogenic avian influenza (HPAI) [FAO]. In this study, we examined the protective efficacy in ducks of two commercial H5N1 vaccines widely used in Vietnam; Re-1 containing A/goose/Guangdong/1/1996 hemagglutinin (HA) clade 0 antigens, and Re-5 containing A/duck/Anhui/1/2006 HA clade 2.3.4 antigens. Ducks received two doses of either vaccine at 7 and at 14 or 21 days of age followed by challenge at 30 days of age with viruses belonging to the HA clades 1.1, 2.3.4.3, 2.3.2.1.A and 2.3.2.1.B isolated between 2008 and 2011 in Vietnam. Ducks vaccinated with the Re-1 vaccine were protected after infection with the two H5N1 HPAI viruses isolated in 2008 (HA clades 1.1 and 2.3.4.3) showing no mortality and limited virus shedding. The Re-1 and Re-5 vaccines conferred 90-100% protection against mortality after challenge with the 2010 H5N1 HPAI viruses (HA clade 2.3.2.1.A); but vaccinated ducks shed virus for more than 7 days after challenge. Similarly, the Re-1 and Re-5 vaccines only showed partial protection against the 2011 H5N1 HPAI viruses (HA clade 2.3.2.1.A and 2.3.2.1.B), with a high proportion of vaccinated ducks shedding virus for more than 10 days. Furthermore, 50% mortality was observed in ducks vaccinated with Re-1 and challenged with the 2.3.2.1.B virus. The HA proteins of the 2011 challenge viruses had the greatest number of amino acid differences from the two vaccines as compared to the viruses from 2008 and 2009, which correlates with the lesser protection observed with these viruses. These studies demonstrate the suboptimal protection conferred by the Re-1 and Re-5 commercial vaccines in ducks against H5N1 HPAI clade 2.3.2.1 viruses, and underscore the importance of monitoring vaccine efficacy in the control of H5N1 HPAI in ducks. Published by Elsevier Ltd.

A comparative analysis of the epidemiological impact and disease cost-savings of HPV vaccines in France

PubMed Central

Bresse, Xavier; Adam, Marjorie; Largeron, Nathalie; Roze, Stephane; Marty, Remi

2013-01-01

The aim was to compare the epidemiological and economic impact of 16/18 bivalent and 6/11/16/18 quadrivalent HPV vaccination in France, considering differences in licensed outcomes, protection against non-vaccine HPV types and prevention of HPV-6/11-related diseases. The differential impact of the two vaccines was evaluated using a published model adapted to the French setting. The target population was females aged 14–23 y and the time horizon was 100 y. A total of eight different scenarios compared vaccination impact in terms of reduction in HPV-16/18-associated carcinomas (cervical, vulvar, vaginal, anal, penile and head and neck), HPV-6/11-related genital warts and recurrent respiratory papillomatosis, and incremental reduction in cervical cancer due to potential cross-protection. Quadrivalent vaccine was associated with total discounted cost savings ranging from EUR 544–1,020 million vs. EUR 177–538 million with the bivalent vaccination (100-y time horizon). Genital wart prevention thanks to quadrivalent HPV vaccination accounted for EUR 306–380 million savings (37–56% of costs saved). In contrast, the maximal assumed cross-protection against cervical cancer resulted in EUR 13–33 million savings (4%). Prevention of vulvar, vaginal and anal cancers accounted for additional EUR 71–89 million savings (13%). In France, the quadrivalent HPV vaccination would result in significant incremental epidemiological and economic benefits vs. the bivalent vaccination, driven primarily by prevention of genital. The present analysis is the first in the French setting to consider the impact of HPV vaccination on all HPV diseases and non-vaccine types. PMID:23563511

Characterization and vaccine potential of Fasciola gigantica saposin-like protein 1 (SAP-1).

PubMed

Kueakhai, Pornanan; Changklungmoa, Narin; Waseewiwat, Pinkamon; Thanasinpaiboon, Thanaporn; Cheukamud, Werachon; Chaichanasak, Pannigan; Sobhon, Prasert

2017-01-15

The recombinant Fasciola gigantica Saposin-like protien-1 (rFgSAP-1) was cloned by polymerase chain reaction (PCR) from NEJ cDNA, expressed in Escherichia coli BL21 (DE3) and used for production of a polyclonal antibody in rabbits (anti-rFgSAP-1). By immunoblotting and immunohistochemistry, rabbit IgG anti-rFgSAP-1 reacted with rFgSAP-1 at a molecular weight 12kDa, but not with rFgSAP-2. The rFgSAP-1 reacted with antisera from mouse infected with F. gigantica metacercariae collected at 2, 4, and 6 weeks after infection. The FgSAP-1 protein was expressed at a high level in the caecal epithelium of metacercariae and NEJs. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rFgSAP-1 combined with Alum adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae per mouse by the oral route. The percents protection of rFgSAP-1 vaccine were estimated to be 73.2% and 74.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. The levels of IgG1 and IgG2a specific to rFgSAP-1 in the immune sera, which are indicative of Th2 and Th1 immune responses, were inversely and significantly correlated with the numbers of worm recoveries. The rFgSAP-1-vaccinated mice showed significantly reduced levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and liver damage. These indicated that rFgSAP-1 has strong potential as a vaccine candidate against F. gigantica, whose efficacy will be studied further in large economic animals including cattle, sheep, and goat. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

PubMed Central

Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

2012-01-01

In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

Immune response to pandemic H1N1 2009 influenza a vaccination in pediatric liver transplant recipients.

PubMed

Haller, Wolfram; Buttery, Jim; Laurie, Karen; Beyerle, Kathe; Hardikar, Winita; Alex, George

2011-08-01

After the announcement of a worldwide pandemic in June 2009, a single dose of a monovalent pandemic H1N1 2009 influenza A (pH1N1/09) vaccine was advocated for all Australians who were 10 years and older because of excellent immunogenicity trial results for healthy children and adults. Immunocompromised patients have previously been shown to have lower seroconversion rates after routine vaccinations. There is a lack of data concerning the immune response of this patient group after pH1N1/09 vaccination. The aim of this study was to assess the immunogenicity of a pH1N1/09 vaccine in pediatric liver transplant recipients 10 years of age or older. Liver transplant recipients ≥ 10 years were prospectively recruited. All participants were administered a single intramuscular injection of the pH1N1/09 vaccine (15 μg). Serum antibody levels were determined by hemagglutination immediately before and ≥ 6 weeks after vaccination. Clinical and laboratory data (age, time since transplantation, immunosuppression, and lymphocyte counts) were analyzed comparing seroconverters and nonconverters with the Student's t test. A second dose of the vaccine was offered to all those who displayed no seroprotective titers after the first vaccination. Antibody levels were again determined 6 weeks later. Twenty-one of 28 liver transplant patients completed the study. The seroconversion rate was 62% after the first dose and 89.5% after the second dose. At baseline, 7 of 21 patients (33.4%) were already seropositive. Increasing time since transplantation positively correlated with successful seroconversion. In conclusion, a single dose of a pandemic influenza A vaccine does not elicit a reliable immune response in adolescent pediatric liver transplant patients. A second dose of the vaccine is warranted in this group of patients, at least in a pandemic scenario. There is an urgent need to further assess vaccine strategies in this high-risk group. Copyright © 2011 American Association for the

H5N1 vaccines in humans

PubMed Central

Baz, Mariana; Luke, Catherine J; Cheng, Xing; Jin, Hong; Subbarao, Kanta

2013-01-01

The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting. PMID:23726847

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men.

PubMed

Van Damme, Pierre; Meijer, Chris J L M; Kieninger, Dorothee; Schuyleman, Anne; Thomas, Stephane; Luxembourg, Alain; Baudin, Martine

2016-07-29

A nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16-26-year-old men. Participants (N=500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed. The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles. In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16-26years. NCT02114385. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

A comparative analysis of vaccine administration in urban and non-urban skilled nursing facilities.

PubMed

Pu, Yuan; Dolar, Veronika; Gucwa, Azad L

2016-07-29

The U.S. population is aging at an unprecedented rate, resulting in an increased demand for skilled nursing facilities (SNFs) and long-term care. Residents of these facilities are at a high risk for pneumococcal disease or severe influenza-related illnesses and death. For these reasons, the Centers for Medicare and Medicaid Services use influenza and pneumococcal vaccination rates as a quality measure in the assessment of SNFs, as complications related to these infections increase morbidity and mortality rates. Disparities have been reported amongst vaccination with increased rates in urban areas as compared to their non-urban counterparts. Statistical analyses were performed to compare influenza and pneumococcal vaccination in urban and non-urban SNFs to determine variables that may influence vaccination status. Of the 15,639 nursing homes included in the study, 10,107 were in urban areas, while 5532 were considered non-urban. We found the percent of eligible and willing residents with up-to-date influenza and pneumococcal vaccinations increased with overall five-star ratings of SNFs. Somewhat paradoxically, although urban SNFs had higher mean overall five-star ratings, they showed lower rates of influenza and pneumococcal vaccination compared to non-urban SNFs. Ordinary least squares regression analysis comparing overall ratings, type of ownership, and geographic location by region yielded statistically significant results in which the overall rating, ownership-type and certificate-type favored urban SNFs (p < 0.001). This is the first systematic and comparative analysis to use the Nursing Home Compare database to assess vaccine administration of urban and non-urban SNFs. The findings of this study may be used to encourage the development of programs to improve vaccination rates and the quality of care in these facilities.

Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys.

PubMed

Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

2016-06-25

Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys

PubMed Central

Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

2016-01-01

Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine. PMID:27348002

[Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

PubMed

Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

2010-12-01

Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Comparative cost models of a liquid nitrogen vapor phase (LNVP) cold chain-distributed cryopreserved malaria vaccine vs. a conventional vaccine

PubMed Central

Garcia, Cristina Reyes; Manzi, Fatuma; Tediosi, Fabrizio; Hoffman, Stephen L.; James, Eric R.

2013-01-01

Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2–8 °C cold chain with 4–5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN2) vapor phase (LNVP) below −140 °C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a ‘conventional’ malaria vaccine through the EPI. Capital and recurrent costs for storage, transportation, labor, energy usage and facilities were determined for the birth cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO calculators. These were applied to a 2–8 °C distribution model with national, regional, district, and health facility levels, and for the cryopreserved vaccine using a ‘modified hub-and-spoke’ (MH-S) LNVP distribution system comprising a central national store, peripheral health facilities and an intermediate district-level transhipment stop. Estimated costs per fully immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine where the LN2 is generated, and $ 6.04 with purchased LN2 (assuming US $ 1.00/L). The FIC costs for distributing a conventional vaccine using the four level 2–8 °C cold chain were $ 6.10, and with a tariff distribution system as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted little difference in 5-year distribution costs between the PfSPZ Vaccine distributed through a MH-S LNVP cold chain and a conventional vaccine distributed through the more traditional EPI system. A LNVP cold chain provides additional benefits through the use of durable dry shippers because no refrigerators, freezers or refrigerated trucks are required. Thus strain at the cold chain periphery, vaccine wastage from cold chain failures and the

Comparative cost models of a liquid nitrogen vapor phase (LNVP) cold chain-distributed cryopreserved malaria vaccine vs. a conventional vaccine.

PubMed

Garcia, Cristina Reyes; Manzi, Fatuma; Tediosi, Fabrizio; Hoffman, Stephen L; James, Eric R

2013-01-02

Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2-8°C cold chain with 4-5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN(2)) vapor phase (LNVP) below -140°C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a 'conventional' malaria vaccine through the EPI. Capital and recurrent costs for storage, transportation, labor, energy usage and facilities were determined for the birth cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO calculators. These were applied to a 2-8°C distribution model with national, regional, district, and health facility levels, and for the cryopreserved vaccine using a 'modified hub-and-spoke' (MH-S) LNVP distribution system comprising a central national store, peripheral health facilities and an intermediate district-level transhipment stop. Estimated costs per fully immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine where the LN(2) is generated, and $ 6.04 with purchased LN(2) (assuming US $ 1.00/L). The FIC costs for distributing a conventional vaccine using the four level 2-8°C cold chain were $ 6.10, and with a tariff distribution system as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted little difference in 5-year distribution costs between the PfSPZ Vaccine distributed through a MH-S LNVP cold chain and a conventional vaccine distributed through the more traditional EPI system. A LNVP cold chain provides additional benefits through the use of durable dry shippers because no refrigerators, freezers or refrigerated trucks are required. Thus strain at the cold chain periphery, vaccine wastage from cold chain failures and the environmental

Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis.

PubMed

Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

2011-09-01

The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection. © 2011 Blackwell Publishing Ltd.

A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients.

PubMed

Elhanan, E; Boaz, M; Schwartz, I; Schwartz, D; Chernin, G; Soetendorp, H; Gal Oz, A; Agbaria, A; Weinstein, T

2018-02-01

Dialysis patients have a suboptimal response to hepatitis B (HBV) vaccination. This study aimed to compare the immunogenicity of two vaccines: the third-generation Sci-B-Vac™ vs. the second-generation Engerix B ® . The cohort included two groups of dialysis patients: naïve and previously vaccinated non-responders. Primary endpoints were antibody titers ≥10 IU/L at 3 and 7 month post-vaccination. Secondary objectives were seroprotection rates in vaccine-naïve patients and in previously vaccinated non-responders. Eighty-six patients were assigned to vaccine (Sci-B-Vac™ or Engerix B ® ) using computer-generated randomization, stratified by age, gender, diabetes, and previous HBV vaccination. Sci-B-Vac™ was administered in three doses, 10 μg, at 0, 1, and 6 months in naïve patients; or 20 μg in previously vaccinated non-responders. Engerix B ® included four doses, 40 μg at 0, 1, 2, and 6 months. Each group had 43 patients. Seroconversion was 69.8% with Engerix B ® vs. 73.2% with Sci-B-Vac™. Antibody titers at 7 months were higher with Sci-B-Vac™ (266.4 ± 383.9, median 53.4) than with Engerix ® (193.2 ± 328.9, median 19). However, these differences were not significant, perhaps due to a suboptimal sample size. This study suggests comparable immunogenicity for both vaccines. Thus, we cannot reject the null hypothesis that there is no difference in seroconversion by vaccine type. It is noteworthy that naïve patients were vaccinated with a standard dose of Sci-B-Vac™, while Engerix B ® was administered at a double dose. Similarly, although mean antibody titer levels in the Sci-B-Vac™ group were higher than in the Engerix ® group, this difference did not reach significance. Consequently, a future clinical trial should recruit a larger cohort of patients, using a standard double-dose protocol in both groups.

Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines

PubMed Central

Dohnal, Alexander Michael; Graffi, Sebastian; Witt, Volker; Eichstill, Christina; Wagner, Dagmar; Ul-Haq, Sidrah; Wimmer, Doris; Felzmann, Thomas

2009-01-01

Abstract Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 ± 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 ± 1%), and a very good purity (92 ± 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 ± 0.4; selection: 20 ± 0.6; depletion: 1 ±0.5; elutriation: 3.6 ± 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 ± 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing. PMID:18363835

Duration of protection against hepatitis A for the current two-dose vaccine compared to a three-dose vaccine schedule in children

PubMed Central

Raczniak, Gregory A.; Thomas, Timothy K.; Bulkow, Lisa R.; Negus, Susan E.; Zanis, Carolyn L.; Bruce, Michael G.; Spradling, Philip R.; Teshale, Eyasu H.; McMahon, Brian J.

2015-01-01

Background Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. Methods We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. Results No significant differences were observed when comparing GMC between the two cohorts at 10 (P = 0.467), 12 (P = 0.496), and 14 (P = 0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years. Conclusion The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term. PMID:23470239

Vaccination with nontoxic mutant toxic shock syndrome toxin 1 protects against Staphylococcus aureus infection.

PubMed

Hu, Dong-Liang; Omoe, Katsuhiko; Sasaki, Sanae; Sashinami, Hiroshi; Sakuraba, Hirotake; Yokomizo, Yuichi; Shinagawa, Kunihiro; Nakane, Akio

2003-09-01

To investigate whether vaccination with nontoxic mutant toxic shock syndrome toxin 1 (mTSST-1) can protect against Staphylococcus aureus infection, mice were vaccinated with mTSST-1 and challenged with viable S. aureus. Survival in the mTSST-1-vaccinated group was higher, and bacterial counts in organs were significantly lower than those of control mice. Passive transfer of mTSST-1-specific antibodies also provided protection against S. aureus-induced septic death. Interferon (IFN)-gamma production in the serum samples and spleens from vaccinated mice was significantly decreased compared with that in controls, whereas interleukin-10 titers were significantly higher in vaccinated mice. IFN-gamma and tumor necrosis factor-alpha production in vitro were significantly inhibited by serum samples from mTSST-1-immunized mice but not from control mice. These results suggest that vaccination with mTSST-1 devoid of superantigenic properties provides protection against S. aureus infection and that the protection might be mediated by TSST-1-neutralizing antibodies as well as by the down-regulation of IFN-gamma production.

Obstetricians and the 2009-2010 H1N1 vaccination effort: implications for future pandemics.

PubMed

Clark, Sarah J; Cowan, Anne E; Wortley, Pascale M

2013-09-01

Our objective was to describe the experiences of obstetricians during the 2009-2010 H1N1 vaccination campaign in order to identify possible improvements for future pandemic situations. We conducted a cross-sectional mail survey of a national random sample of 4,000 obstetricians, fielded in Summer 2010. Survey items included availability, recommendation, and patient acceptance of H1N1 vaccine; prioritization of H1N1 vaccine when supply was limited; problems with H1N1 vaccination; and likelihood of providing vaccine during a future influenza pandemic. Response rate was 66 %. Obstetricians strongly recommended H1N1 vaccine during the second (85 %) and third (86 %) trimesters, and less often during the first trimester (71 %) or the immediate postpartum period (76 %); patient preferences followed a similar pattern. H1N1 vaccine was typically available in outpatient obstetrics clinics (80 %). Overall vaccine supply was a major problem for 30 % of obstetricians, but few rated lack of thimerosal-free vaccine as a major problem (12 %). Over half of obstetricians had no major problems with the H1N1 vaccine campaign. Based on this experience, 74 % would be "very likely" and 12 % "likely" to provide vaccine in the event of a future influenza pandemic. Most obstetricians strongly recommended H1N1 vaccine, had few logistical problems beyond limited vaccine supply, and are willing to vaccinate in a future pandemic. Addressing concerns about first-trimester vaccination, developing guidance for prioritization of vaccine in the event of severe supply constraints, and continued facilitation of the logistical aspects of vaccination should be emphasized in future influenza pandemics.

Clinical efficacy of seasonal influenza vaccination: characteristics of two outbreaks of influenza A(H1N1) in immunocompromised patients.

PubMed

Helanterä, I; Janes, R; Anttila, V-J

2018-06-01

Influenza A(H1N1) causes serious complications in immunocompromised patients. The efficacy of seasonal vaccination in these patients has been questioned. To describe two outbreaks of influenza A(H1N1) in immunocompromised patients. Two outbreaks of influenza A(H1N1) occurred in our institution: on the kidney transplant ward in 2014 including patients early after kidney or simultaneous pancreas-kidney transplantation, and on the oncology ward in 2016 including patients receiving chemotherapy for malignant tumours. Factors leading to these outbreaks and the clinical efficacy of seasonal influenza vaccination were analysed. Altogether 86 patients were exposed to influenza A(H1N1) during the outbreaks, among whom the seasonal influenza vaccination status was unknown in 10. Only three out of 38 vaccinated patients were infected with influenza A(H1N1), compared with 20 out of 38 unvaccinated patients (P = 0.02). The death of one out of 38 vaccinated patients was associated with influenza, compared with seven out of 38 unvaccinated patients (P = 0.06). Shared factors behind the two outbreaks included outdated facilities not designed for the treatment of immunosuppressed patients. Vaccination coverage among patients was low, between 40% and 70% despite vaccination being offered to all patients free of charge. Vaccination coverage of healthcare workers on the transplant ward was low (46%), but, despite high coverage on the oncology ward (92%), the outbreak occurred. Seasonal influenza vaccination was clinically effective with both a reduced risk of influenza infection and a trend towards reduced mortality in these immunocompromised patients. Several possible causes were identified behind these two outbreaks, requiring continuous awareness in healthcare professionals to prevent further outbreaks. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Antibody response to influenza A(H1N1)pdm09 among healthcare personnel receiving trivalent inactivated vaccine: effect of prior monovalent inactivated vaccine.

PubMed

Gaglani, Manjusha; Spencer, Sarah; Ball, Sarah; Song, Juhee; Naleway, Allison; Henkle, Emily; Bozeman, Sam; Reynolds, Sue; Sessions, Wendy; Hancock, Kathy; Thompson, Mark

2014-06-01

Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010-2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥ 40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72-3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84-.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65-.88]), 52% among those who received MIIV only, and 12% among those receiving neither. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

PubMed Central

Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C.; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

2016-01-01

The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience.

PubMed

Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène; Gudlaugsson, Ólafur; Hauge, Siri Helene; Lyytikäinen, Outi; Sigmundsdóttir, Guðrún; Tegnell, Anders; Virtanen, Mikko; Krause, Tyra Grove

2016-04-21

During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9-3.0) and deaths (IRR: 8.3; 95% CI: 5.1-13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

Key points in evaluating immunogenicity of pandemic influenza vaccines: A lesson from immunogenicity studies of influenza A(H1N1)pdm09 vaccine.

PubMed

Ohfuji, Satoko; Kobayashi, Masayuki; Ide, Yuichiro; Egawa, Yumi; Saito, Tomoko; Kondo, Kyoko; Ito, Kazuya; Kase, Tetsuo; Maeda, Akiko; Fukushima, Wakaba; Hirota, Yoshio

2017-09-18

Immunogenicity studies on pandemic influenza vaccine are necessary to inform rapid development and implementation of a vaccine during a pandemic. Thus, strategies for immunogenicity assessment are required. To identify essential factors to consider when evaluating the immunogenicity of pandemic influenza vaccines using the experience in Japan with the influenza A(H1N1)pdm09 vaccine. We conducted a search of observational studies using PubMed and IchushiWeb. Search terms included "influenza vaccine AND (immunogenicity OR immune response) AND Japan AND (2009 OR pdm09) NOT review," and was limited to studies conducted in humans. A total of 33 articles were identified, of which 16 articles met the inclusion criteria. Immunogenicity of the commercially available influenza A(H1N1)pdm09 vaccine satisfied the international criteria for influenza vaccine immunogenicity in all study populations. The most remarkable immune response was observed in junior high school students, while the lowest immune response was observed in hematological malignancy patients. Similar to immunogenicity studies on seasonal influenza vaccines, factors such as patient background (e.g., age, underlying condition, pre-vaccination titer, body mass index, etc.) and study procedure (e.g., concurrent measurement of pre- and post-vaccination antibody titer, effects of infection during the study period) may have affected the assessment of immunogenicity to the influenza A(H1N1)pdm09 vaccine. In addition, prior vaccination with the seasonal influenza vaccine may inhibit antibody induction by the influenza A(H1N1)pdm09 vaccine. This review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A comparative study of the incidence of aseptic meningitis in symptomatic natural mumps patients and monovalent mumps vaccine recipients in Japan.

PubMed

Nagai, Takao; Okafuji, Teruo; Miyazaki, Chiaki; Ito, Yuhei; Kamada, Makoto; Kumagai, Takuji; Yuri, Kenji; Sakiyama, Hiroshi; Miyata, Akiko; Ihara, Toshiaki; Ochiai, Hitoshi; Shimomura, Kunihisa; Suzuki, Eitaro; Torigoe, Sadayoshi; Igarashi, Masahiro; Kase, Tetsuo; Okuno, Yoshinobu; Nakayama, Tetsuo

2007-03-30

To compare the incidence of aseptic meningitis associated with symptomatic natural mumps infection and in mumps vaccine recipients, we conducted a prospective comparative study. Consecutive samples of 1051 children with mumps were enrolled by 10 pediatricians and 21,465 vaccine recipients by 143 pediatric primary care practitioners, from January 1, 2000 to January 1, 2003. Parents used a daily diary to record symptoms during the period of illness (15 days) or 30-day period following immunization. Mumps infection was confirmed by virus isolation and/or detection of mumps virus genome in salivary and CSF samples. The incidence of aseptic meningitis was 13/1051 (1.24%) in patients with symptomatic natural mumps infection and was estimated to be 0.7-1.1% of overall infection in considering asymptomatic infection, and 10/21,465 (0.05%) in vaccine recipients. Although aseptic meningitis is a clear side effect of the mumps vaccine, the incidence is considerably lower than among those with symptomatic natural infection. Our results provide an informative data for consideration to resume mumps vaccine as a part of routine immunization schedule for Japanese children.

Vaccine-Induced Env V1–V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination

PubMed Central

Yates, Nicole L.; Liao, Hua-Xin; Fong, Youyi; deCamp, Allan; Vandergrift, Nathan A.; Williams, William T.; Alam, S. Munir; Ferrari, Guido; Yang, Zhi-yong; Seaton, Kelly E.; Berman, Phillip W.; Alpert, Michael D.; Evans, David T.; O’Connell, Robert J.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Tartaglia, James; Pinter, Abraham; Zolla-Pazner, Susan; Gilbert, Peter B.; Nabel, Gary J.; Michael, Nelson L.; Kim, Jerome H.; Montefiori, David C.; Haynes, Barton F.; Tomaras, Georgia D.

2014-01-01

HIV-1–specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1–specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1–specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials. PMID:24648342

Stochastic simulation model comparing distributions of STEC O157 faecal shedding prevalence between cattle vaccinated with type III secreted protein vaccines and non-vaccinated cattle.

PubMed

Vogstad, A R; Moxley, R A; Erickson, G E; Klopfenstein, T J; Smith, D R

2014-06-01

Pens of cattle with high Escherichia coli O157:H7 (STEC O157) prevalence at harvest may present a greater risk to food safety than pens of lower prevalence. Vaccination of live cattle against STEC O157 has been proposed as an approach to reduce STEC O157 prevalence in live cattle. Our objective was to create a stochastic simulation model to evaluate the effectiveness of pre-harvest interventions. We used the model to compare STEC O157 prevalence distributions for summer- and winter-fed cattle to summer-fed cattle immunized with a type III secreted protein (TTSP) vaccine. Model inputs were an estimate of vaccine efficacy, observed frequency distributions for number of animals within a pen, and pen-level faecal shedding prevalence for summer and winter. Uncertainty about vaccine efficacy was simulated using a log-normal distribution (mean = 58%, SE = 0.14). Model outputs were distributions of STEC O157 faecal pen prevalence of summer-fed cattle unvaccinated and vaccinated, and winter-fed cattle unvaccinated. The simulation was performed 5000 times. Summer faecal prevalence ranged from 0% to 80% (average = 30%). Thirty-six per cent of summer-fed pens had STEC O157 prevalence >40%. Winter faecal prevalence ranged from 0% to 60% (average = 10%). Seven per cent of winter-fed pens had STEC O157 prevalence >40%. Faecal prevalence for summer-fed pens vaccinated with a 58% efficacious vaccine product ranged from 0% to 52% (average = 13%). Less than one per cent of vaccinated pens had STEC O157 prevalence >40%. In this simulation, vaccination mitigated the risk of STEC O157 faecal shedding to levels comparable to winter, with the major effects being reduced average shedding prevalence, reduced variability in prevalence distribution, and a reduction in the occurrence of the highest prevalence pens. Food safety decision-makers may find this modelling approach useful for evaluating the value of pre-harvest interventions. © 2013 Blackwell Verlag GmbH.

Risk of Guillain–Barré syndrome following pandemic influenza A(H1N1) 2009 vaccination in Germany†

PubMed Central

Prestel, Jürgen; Volkers, Peter; Mentzer, Dirk; Lehmann, Helmar C; Hartung, Hans-Peter; Keller-Stanislawski, Brigitte

2014-01-01

Purpose A prospective, epidemiologic study was conducted to assess whether the 2009 pandemic influenza A(H1N1) vaccination in Germany almost exclusively using an AS03-adjuvanted vaccine (Pandemrix) impacts the risk of Guillain–Barré syndrome (GBS) and its variant Fisher syndrome (FS). Methods Potential cases of GBS/FS were reported by 351 participating hospitals throughout Germany. The self-controlled case series methodology was applied to all GBS/FS cases fulfilling the Brighton Collaboration (BC) case definition (levels 1–3 of diagnostic certainty) with symptom onset between 1 November 2009 and 30 September 2010 reported until end of December 2010. Results Out of 676 GBS/FS reports, in 30 cases, GBS/FS (BC levels 1–3) occurred within 150 days following influenza A(H1N1) vaccination. The relative incidence of GBS/FS within the primary risk period (days 5–42 post-vaccination) compared with the control period (days 43–150 post-vaccination) was 4.65 (95%CI [2.17, 9.98]). Similar results were found when stratifying for infections within 3 weeks prior to onset of GBS/FS and when excluding cases with additional seasonal influenza vaccination. The overall result of temporally adjusted analyses supported the primary finding of an increased relative incidence of GBS/FS following influenza A(H1N1) vaccination. Conclusions The results indicate an increased risk of GBS/FS in temporal association with pandemic influenza A(H1N1) vaccination in Germany. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24817531

Did Rev-1 small ruminants vaccination helped improve cattle brucellosis prevalence status in Algeria?

PubMed

Kardjadj, Moustafa

2017-12-01

In 2006, the Algerian authorities started the Rev-1 vaccination of sheep and goats; consequently, there was a significant improvement of small ruminant brucellosis sanitary status. In this paper, we attempt to study the effect of Rev-1 small ruminants' vaccination on cattle brucellosis prevalence in Algeria. Our results showed an overall cattle herd seroprevalence of 12% (9 positive herds of 75). The risk factor analysis using a logistic regression model indicated that the presence of small ruminants along with cattle in the herd (mixed herds) decreased the odds for brucellosis seropositivity by 1.69 [95% CI 0.54-2.84; P = 0.042] compared to the cattle herds only. Likewise, the present study showed that the presence of Rev-1 vaccinated small ruminants in the herd decreased also the odds for brucellosis seropositivity by 4.10 [95% CI 3.20-5.00; P = 0.003] compared to other herds. This result lead to the assumption that the small ruminants Rev-1 vaccination diminish Brucella microbisme pressure in the mixed herds and help decrease the cattle brucellosis prevalence in these herds.

Analysis of porcine circovirus type 1 detected in Rotarix vaccine.

PubMed

Baylis, Sally A; Finsterbusch, Tim; Bannert, Norbert; Blümel, Johannes; Mankertz, Annette

2011-01-17

A metagenomic analysis of live human vaccines has recently demonstrated the presence of porcine circovirus type 1 (PCV1) DNA in the paediatric vaccine Rotarix used in the prevention of acute gastroenteritis. Using real-time PCR for PCV1, titres of PCV1 DNA in several batches of Rotarix were found to be in the order of 6-7 log(10) copies per dose. Pre-treatment of the reconstituted vaccine with the nuclease Benzonase, followed by extraction of nucleic acid and quantification of PCV1 DNA by real-time PCR, revealed that there was no loss of PCV1 DNA titre compared to untreated controls, suggesting that the porcine viral DNA was present in the vaccine in an encapsidated form. PCV1 permissive PS cells, human HEK293 and Vero cells, used for vaccine production, were infected with Rotarix or PCV1, respectively, and subjected to immune fluorescence and RT-PCR. Viral genomes were present in Rotarix-incubated as well as PCV1-infected cells, while viral transcription was seen only in PCV1-infected cells. Similarly, PCV1-specific protein expression was observed in PCV1-infected cells, but not in cells treated with Rotarix. Passaging of the supernatant indicated productive infection in PCV1-infected PS cells, but not in HEK293 and Vero cells or in any cell line incubated with Rotarix. PCV1 DNA present in Rotarix was protected from Benzonase digestion; however, PCV1 was not recognized in immune electron microscopy and unable to infect PS, HEK293 or Vero cells, suggesting that the high amount of PCV1 DNA present in Rotarix does not reflect a corresponding proportion of biologically active virus particles. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population.

PubMed

Ong, Gary; Goh, Kee Tai; Ma, Stefan; Chew, Suok Kai

2005-11-01

The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore. Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated. The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively. Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.

Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses

PubMed Central

Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold

2016-01-01

ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head

Measuring HPV vaccination coverage in Australia: comparing two alternative population-based denominators.

PubMed

Barbaro, Bianca; Brotherton, Julia M L

2015-08-01

To compare the use of two alternative population-based denominators in calculating HPV vaccine coverage in Australia by age groups, jurisdiction and remoteness areas. Data from the National HPV Vaccination Program Register (NHVPR) were analysed at Local Government Area (LGA) level, by state/territory and by the Australian Standard Geographical Classification Remoteness Structure. The proportion of females vaccinated was calculated using both the ABS ERP and Medicare enrolments as the denominator. HPV vaccine coverage estimates were slightly higher using Medicare enrolments than using the ABS estimated resident population nationally (70.8% compared with 70.4% for 12 to 17-year-old females, and 33.3% compared with 31.9% for 18 to 26-year-old females, respectively.) The greatest differences in coverage were found in the remote areas of Australia. There is minimal difference between coverage estimates made using the two denominators except in Remote and Very Remote areas where small residential populations make interpretation more difficult. Adoption of Medicare enrolments for the denominator in the ongoing program would make minimal, if any, difference to routine coverage estimates. © 2015 Public Health Association of Australia.

Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life.

PubMed

Vaarala, Outi; Jokinen, Jukka; Lahdenkari, Mika; Leino, Tuija

2017-07-01

Rotavirus infection has been suggested as a trigger of type 1 diabetes (T1D)-related autoimmunity and celiac disease (CD)-related autoimmunity. We carried out a nationwide, population-based cohort study evaluating whether prevention of rotavirus infection with vaccination affects the risk of CD and T1D diagnosed during 2009-2014 in Finnish children by comparing vaccinated and unvaccinated children in a cohort born in 2009-2010. Nationwide rotavirus vaccination records were collected from healthcare databases during 2009-2011 and validated for a sample of 495 children born from July 2009 to December 2009. Incident diagnoses of CD and T1D during 2009-2014 in the cohort were identified in the National Care Register. The adjusted relative risks (with 95% confidence intervals) were 0.91 (0.69-1.20) for T1D and 0.87 (0.65-1.17) for CD in vaccinated children compared with unvaccinated, suggesting that oral rotavirus vaccination does not alter the risk of CD or T1D during 4-6 years follow-up after vaccination. Our results suggest that oral rotavirus vaccination is considered safe in the individuals at risk of CD and T1D.

A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

PubMed

García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

2012-05-28

Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optimal H1N1 vaccination strategies based on self-interest versus group interest.

PubMed

Shim, Eunha; Meyers, Lauren Ancel; Galvani, Alison P

2011-02-25

Influenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for pandemic influenza, public health agencies need to consider

Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients.

PubMed

Beaudreuil, Séverine; Krivine, Anne; Hebibi, Hadia; Ducot, Béatrice; Mazet, Anne-Aurélie; Taouffik, Yacine; Seidowsky, Alexandre; Jacquet, Antoine; Lorenzo, Hans Kristian; Charpentier, Bernard; Francois, Hélène; Durrbach, Antoine

2011-08-01

The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients. 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion). Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs. Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs.

The safety of H1N1 vaccine in children in Saudi Arabia: a cohort study using modern technology in a developing country.

PubMed

Aljadhey, Hisham; Alyabsi, Mesnad; Alrwisan, Adel; Alqahtani, Nasser; Almutairi, Reem; Al Tawil, Esraa; Adam, Mansour; Shakir, Saad; Aljeraisy, Majed; Al-Blowi, Ali; Alkhashan, Hesham; Albogami, Yasser; Murray, Michael D

2012-07-01

With its rapid introduction in 2009, concerns about the safety of the H1N1 vaccines have been raised. Data were especially limited on the pediatric safety of H1N1 vaccine in Saudi Arabia. The objectives of this study were to investigate the safety of the H1N1 vaccine (Pandemrix(®)) in children and examine the feasibility of obtaining information on possibly associated adverse reactions using mobile telephone contact with child caregivers. A cohort study was conducted in Riyadh, Saudi Arabia. Patients were included if they were aged between 6 and 18 years and had received one dose of the H1N1 vaccine. A control group involved children from the same school system who had not received the vaccine. Six months following vaccination, a clinical pharmacist called the caregiver of the child to ask about hospitalization, emergency room visits and events related to H1N1 vaccine administration using a standardized questionnaire. Caregivers of 372 school-age children were contacted. The response rate was 97% (n = 359). A total of 169 children who received at least one dose of the H1N1 vaccine were compared with 190 children in the control group who had not received the vaccine. Controlling for age, sex, education and use of medications, the odds ratio (OR) of hospitalization or emergency room visits for children within the 6 months after vaccination relative to the unvaccinated children was 1.25 (95% CI 0.47, 3.35). The risk of influenza-like symptoms was significantly reduced in vaccinated children compared with unvaccinated children (OR 0.63; 95% CI 0.41, 0.99). School-age children in Saudi Arabia who received the H1N1 vaccine did not have an increased risk of hospitalization or emergency room visits. Larger studies are needed to confirm these results. Proactive pharmacovigilance is important in assessing the safety of vaccines and other medications. It is feasible to collect information on adverse drug reactions using mobile telephones, a method that can be of benefit in

Social regulations predispose people to complete vaccination for vaccine-preventable diseases.

PubMed

Takeuchi, Jiro; Goto, Masashi; Kawamura, Takashi; Hiraide, Atsushi

2014-11-01

Japan experienced measles outbreaks in both 2006 and 2007 mainly among university students. Improvement of vaccine coverage against vaccine-preventable viral infections is the prime task for preventing outbreaks of viral infections. To elucidate the promoting factors for complete vaccination against measles, rubella, mumps, and varicella-zoster viruses, we conducted a case-control study among single university students in Japan. Information on vaccinations and clinico-demographical factors were collected using a self-administered questionnaire and a photocopy of the Maternal and Child Health Handbook. Logistic regression analysis was performed to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for two-time vaccination against measles and rubella viruses as mandatory vaccinations and at least one-time vaccination against mumps and varicella-zoster viruses as optional vaccinations. A total of 1,370 (744 medical, 508 paramedical, and 118 pharmaceutical) students were invited to participate, 960 (70.1%) of whom were enrolled in the study. Students aged < 20 years had a greater propensity for measles and rubella vaccinations (OR 7.8 [95% CI, 5.1-11.8] and OR 6.1 [95% CI, 3.7-10.0], respectively) compared with those aged ≥ 20 years. Students with a history of living over-seas for 1 month or longer were more likely to complete vaccination for measles (OR 4.4 [95% CI, 1.4-13.5] compared with those without such history. This significantly high vaccination coverage was attributed to the measles-rubella catch-up campaign by the Japanese government and the immunization regulations by foreign countries. These findings suggest that social regulations would predispose people to complete vaccination.

2.097μ Cth:YAG flashlamp pumped high energy high efficiency laser operation (patent pending)

NASA Astrophysics Data System (ADS)

Bar-Joseph, Dan

2018-02-01

Flashlamp pumped Cth:YAG lasers are mainly used in medical applications (urology). The main laser transition is at 2.13μ and is called a quasi-three level having an emission cross-section of 7x10-21 cm2 and a ground state absorption of approximately 5%/cm. Because of the relatively low absorption, combined with a modest emission cross-section, the laser requires high reflectivity output coupling, and therefore high intra-cavity energy density which limits the output to approximately 4J/pulse for reliable operation. This paper will describe a method of efficiently generating high output energy at low intra-cavity energy density by using an alternative 2.097μ transition having an emission cross-section of 5x10-21 cm2 and a ground level absorption of approximately 14%/cm.

Comparative safety and efficacy of subcutaneous and intradermal administration of inactivated Japanese encephalitis vaccine during predeployment preparations in the Australian Defence Force.

PubMed

Kitchener, Scott; Nasveld, Peter; Brennan, Len; Ward, David

2006-12-01

Japanese encephalitis is a viral disease emerging in areas of influence for the Australian Defence Force immediately north of the continent, including the Torres Strait border of Australia and Papua, New Guinea. Only the mouse brain-derived, inactivated, Nakayama strain vaccine is commercially available to the Australian Defence Force. This vaccine has a high cost and significant adverse event profile, requiring restricted duties after administration. To address these issues, intradermal vaccination (either single intradermal administration or two intradermal injections at two separate sites) was assessed, compared with the conventional subcutaneous vaccination method, in a randomized controlled trial among soldiers preparing for deployment. Dual intradermal vaccination (0.1 mL at two sites) was found to have a slightly more favorable adverse event profile while maintaining comparable serological efficacy and reduced cost. An expansion of the concept and a test of logistics were conducted by vaccinating a battalion formation during predeployment medical preparations. The method of vaccination was well accepted and retained comparable immunogenicity.

The decision to vaccinate or not during the H1N1 pandemic: selecting the lesser of two evils?

PubMed

Ashbaugh, Andrea R; Herbert, Christophe F; Saimon, Elena; Azoulay, Nelson; Olivera-Figueroa, Lening; Brunet, Alain

2013-01-01

With the release of the H1N1 vaccine, there was much controversy surrounding its use despite strong encouragements to be vaccinated in the media. Though studies have examined factors influencing people's decision to be vaccinated, few have focused on how general beliefs about the world or where an individual gathers information might influence that decision. A cross-sectional web-based survey (N = 817) was conducted during the H1N1 outbreak after the vaccine was available. Variables examined included sociodemographic information, health related behaviours, specific beliefs concerning the H1N1 virus and its vaccine, as well as general beliefs, such as fear of contamination, intolerance of uncertainty, emotional states, coping behaviour, and the source of information concerning the virus. Three converging statistical methods were used to examine the associations - analysis of variance, logistic regression, and recursive partition modelling. The most consistent and strongest association was that negative beliefs about the H1N1 vaccine (e.g. fear of its side effects) was related to the decision not to be vaccinated, whereas beliefs about the dangers of the H1N1 virus was related to the decision to be vaccinated. Most notably, having very strong negative beliefs about the vaccine was a more powerful predictor than even strong beliefs about the dangers of the H1N1 virus. Furthermore, obtaining information from the Internet, as compared to more traditional sources of information (e.g., TV, newspapers) was related to the decision not to be vaccinated. These results are consistent with the Health Belief Model. Importantly they suggest that during future pandemics public health officials should not only discuss the dangers of the pandemic but also (i) take additional steps to reassure the public about the safety of vaccines and (ii) monitor the information disseminated over the Internet rather than strictly relying on the more traditional mass media.

First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.

PubMed

Lindgren, Line M; Tingskov, Pernille N; Justesen, Annette H; Nedergaard, Bettina S; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit

2017-01-23

There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447. Copyright © 2016. Published by Elsevier Ltd.

Acceptance of H1N1 vaccine among healthcare workers at primary healthcare centres in Abha, KSA.

PubMed

Alsaleem, Mohammed Abadi

2013-04-01

One of the major concerns related to the pandemic outbreak of H1N1 influenza in 2009 was the cost burden on medical resources, which led to a negative impact on mortality and morbidity. This situation placed healthcare workers (HCWs) in an unusual position of being both the main actors and one of the main targets of the prevention strategies against the 2009 pandemic influenza A (H1N1). The aim of the study was to find out and compare the acceptance of H1N1 vaccine among different categories of primary HCWs in primary healthcare centres in Abha as well as to explore the reasons among them for not accepting the HINI vaccine. A cross-sectional study was conducted including all HCWs serving at primary healthcare centres in Abha. A self-administered validated questionnaire was used to collect data reflecting the intake of H1N1 vaccine and its association with other parameters that may influence the uptake of this vaccine. The overall response rate was 347/402 (86.3%). The age of the participants ranged between 22 and 59 years with a mean of 34.9 years and SD of 8.4 years. The percentage of physicians, nurses and technicians who took the H1N1 vaccination was 32.6, 28 and 10%, respectively. The overall vaccine intake rate was 28.2%. The main reasons given by HCWs for being immunized were personal protection (51%), fear of transmitting disease to their family and relatives (49%) and fear of transmitting the disease to their patients (43.9%). The main reasons given by HCWs for rejecting H1N1 vaccination were fear of side effects (70.3%) and doubts regarding the safety of the vaccine (68.3%). In general, knowledge about H1N1 was insufficient. However, it was better among physicians than among nurses and technicians. The low rate of acceptance of the pandemic vaccine and the insufficient level of knowledge about the H1N1 virus among Saudi HCWs were alarming given that they were considered models for patients and the public.

Gallid herpesvirus 3 SB-1 strain as a recombinant viral vector for poultry vaccination.

PubMed

Sadigh, Yashar; Powers, Claire; Spiro, Simon; Pedrera, Miriam; Broadbent, Andrew; Nair, Venugopal

2018-01-01

Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines. Gallid herpesvirus 3 (GaHV3) strain SB-1 is widely used by the poultry industry as bivalent vaccine in combination with HVT to exploit synergistic effects against MD. Here, we report the development and application of SB-1 as a vaccine vector to express the VP2 capsid antigen of IBD virus. A VP2 expression cassette was introduced into the SB-1 genome at three intergenic locations (UL3/UL4, UL10/UL11 and UL21/UL22) using recombineering methods on the full-length pSB-1 infectious clone of the virus. We show that the recombinant SB-1 vectors expressing VP2 induced neutralising antibody responses at levels comparable to that of commercial HVT-based VAXXITEK HVT+IBD vaccine. Birds vaccinated with the experimental recombinant SB-1 vaccine were protected against clinical disease after challenge with the very virulent UK661 IBDV isolate, demonstrating its value as an efficient viral vector for developing multivalent vaccines against avian diseases.

Pandemic influenza A (H1N1) 2009 vaccine: an update.

PubMed

Goel, M K; Goel, M; Khanna, P; Mittal, K

2011-01-01

The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.

Vaccination Rates among Adolescents in Minnesota as Compared with the United States: Not "Above Average".

PubMed

Jacobson, Robert M; Rogacki, Brianna; Thompson, David M; Roberts, James R; Margolis, Benyamin; Darden, Paul M

2015-01-01

Because adolescents make relatively few visits to clinics for preventive care, their vaccination rates suffer. We examined rates among Minnesota youths to see how they compared with those among teens throughout the United States. We used National Immunization Survey-Teen (NIS-Teen) data to estimate vaccination rates for 13- to 17-year-olds in Minnesota from 2008 through 2013 and compared them to national rates for MCV4, Tdap and HPV vaccines. We also examined rates of provider recommendation for each of the three vaccines and rates of parental intention to vaccinate against HPV. We found rates for all three vaccinations increased between 2008 and 2013, but they continue to be low for both MCV4 (69%) and HPV (38% of females and 9% of males completed the three-dose series in 2013). Fortunately, the percentage of Minnesota clinicians recommending those vaccines is increasing (the percentage recommending HPV vaccination for females increased from 55% in 2008 to 74% in 2013; however, only 44% recommended it for males in 2013). The percentage of parents in Minnesota reporting intent to vaccinate their female children against HPV rose from 52% in 2008 to 58% in 2013; the percentage intending to vaccinate their male children rose from 16% in 2010 to 47% in 2013. Clinicians and public health officials must address how we can improve HPV vaccination rates among adolescents.

Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

PubMed

Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

2016-08-15

In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

PubMed

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

PubMed

Holubar, Marisa; Stavroulakis, Maria Christina; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina

2017-01-01

Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

PubMed Central

Maldonado, Yvonne; Ioannidis, John P. A.; Contopoulos-Ioannidis, Despina

2017-01-01

Background Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. Methods We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. Results We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the

A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults.

PubMed

Ma, Jingchen; Wang, Hongchang; Li, Jun; Chang, Likuan; Xie, Yun; Liu, Zhonglin; Zhao, Yuliang; Malerczyk, Claudius; Claudius, Malerczyk

2014-01-01

The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance.

A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults

PubMed Central

Ma, Jingchen; Wang, Hongchang; Li, Jun; Chang, Likuan; Xie, Yun; Liu, Zhonglin; Zhao, Yuliang; Claudius, Malerczyk

2014-01-01

The Zagreb regimen has been used for 20 years in various countries. In China, until 2010, the Zagreb schedule was only approved for purified chick embryo cell vaccine (PCECV) and purified Vero cell rabies vaccines (PVRV). In this phase III clinical trial, we aimed to demonstrate the safety and immunogenic non-inferiority of the Zagreb regimen compared with the Essen regimen in healthy adult Chinese immunized with PCECV (Rabipur®). The study enrolled 825 subjects aged 18 to 50 years; serum samples were collected on Days 0, 7, 14, 42, and at 13 months to assess rabies virus neutralizing antibody (RVNA) concentrations. Solicited and unsolicited local and systemic reactions were recorded for 6 days following the day of vaccination, and collected throughout the entire study period (Day 1 until Month 13). The Zagreb regimen was non-inferior to the Essen regimen with regard to RVNA concentrations after 7, 14, and 42 days, and 13 months of immunization. The non-inferiority of seroconversion was established at Days 14 and 42. The incidence of local and systemic reactions was similar between groups, and mostly of mild or moderate severity. Vaccine-related adverse events occurred more frequently in the Essen group than in the Zagreb group. Vaccination with PCECV under a 2-1-1 regimen is as safe and immunogenic as under the traditional 5-dose Essen regimen for rabies post-exposure prophylaxis, and is a more cost-effective option, has a more practical vaccination schedule, and can potentially increase compliance. PMID:25483635

Factors Mediating Seasonal and Influenza A (H1N1) Vaccine Acceptance among Ethnically Diverse Populations in the Urban South

PubMed Central

Frew, Paula M.; Painter, Julia E.; Hixson, Brooke; Kulb, Carolyn; Moore, Kathryn; del Rio, Carlos; Esteves-Jaramillo, Alejandra; Omer, Saad B.

2012-01-01

Objective We examined the acceptability of the influenza A (H1N1) and seasonal vaccinations immediately following government manufacture approval to gauge potential product uptake in minority communities. We studied correlates of vaccine acceptance including attitudes, beliefs, perceptions, and influenza immunization experiences, and sought to identify communication approaches to increase influenza vaccine coverage in community settings. Methods Adults ≥ 18 years participated in a cross-sectional survey from September through December 2009. Venue-based sampling was used to recruit participants of racial and ethnic minorities. Results The sample (N=503) included mostly lower income (81.9%, n=412) participants and African Americans (79.3%, n=399). Respondents expressed greater acceptability of the H1N1 vaccination compared to seasonal flu immunization (t=2.86, p=0.005) although H1N1 vaccine acceptability was moderately low (38%, n=191). Factors associated with acceptance of the H1N1 vaccine included positive attitudes about immunizations [OR=0.23, CI (0.16, 0.33)], community perceptions of H1N1 [OR=2.15, CI (1.57, 2.95)], and having had a flu shot in the past 5 years [OR=2.50, CI (1.52, 4.10). The factors associated with acceptance of the seasonal flu vaccine included positive attitudes about immunization [OR=0.43, CI (0.32, 0.59)], community perceptions of H1N1 [OR=1.53, CI (1.16, 2.01)], and having had the flu shot in the past 5 years [OR=3.53, CI (2.16, 5.78)]. Participants were most likely to be influenced to take a flu shot by physicians [OR=1.94, CI (1.31, 2.86)]. Persons who obtained influenza vaccinations indicated that Facebook (χ2=11.7, p=.02) and Twitter (χ2=18.1, p=.001) could be useful vaccine communication channels and that churches (χ2=21.5, p<.001) and grocery stores (χ2=21.5, p<.001) would be effective “flu shot stops” in their communities. Conclusions In this population, positive vaccine attitudes and community perceptions, along with

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

PubMed Central

Black, Steven; Eskola, Juhani; Siegrist, Claire-Anne; Halsey, Neal; MacDonald, Noni; Law, Barbara; Miller, Elizabeth; Andrews, Nick; Stowe, Julia; Salmon, Daniel; Vannice, Kirsten; Izurieta, Hector S; Akhtar, Aysha; Gold, Mike; Oselka, Gabriel; Zuber, Patrick; Pfeifer, Dina; Vellozzi, Claudia

2010-01-01

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21·5 cases of Guillain-Barré syndrome and 5·75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86·3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. PMID:19880172

Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

PubMed

Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2015-12-01

We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

PubMed Central

Lefevre, Eric A.; Carr, B. Veronica; Inman, Charlotte F.; Prentice, Helen; Brown, Ian H.; Brookes, Sharon M.; Garcon, Fanny; Hill, Michelle L.; Iqbal, Munir; Elderfield, Ruth A.; Barclay, Wendy S.; Gubbins, Simon; Bailey, Mick; Charleston, Bryan

2012-01-01

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions. PMID:22427834

HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1.

PubMed

Hertz, Tomer; Ahmed, Hasan; Friedrich, David P; Casimiro, Danilo R; Self, Steven G; Corey, Lawrence; McElrath, M Juliana; Buchbinder, Susan; Horton, Helen; Frahm, Nicole; Robertson, Michael N; Graham, Barney S; Gilbert, Peter

2013-01-01

Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different

Comparative effectiveness of different strategies of oral cholera vaccination in bangladesh: a modeling study.

PubMed

Dimitrov, Dobromir T; Troeger, Christopher; Halloran, M Elizabeth; Longini, Ira M; Chao, Dennis L

2014-12-01

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1-14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

PubMed Central

Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

2014-01-01

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

PubMed Central

Hossain, Md Kamal; Wall, Katherine A.

2016-01-01

Aberrantly glycosylated mucin 1 (MUC1) is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012. PMID:27472370

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.

PubMed

Morgan, Eileen; Halliday, Sophia R; Campbell, Gemma R; Cardwell, Chris R; Patterson, Chris C

2016-02-01

The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible. A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis. In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs. This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Prevention of abortion in cattle following vaccination against bovine herpesvirus 1: A meta-analysis.

PubMed

Newcomer, Benjamin W; Cofield, L Grady; Walz, Paul H; Givens, M Daniel

2017-03-01

Bovine herpesvirus 1 is ubiquitous in cattle populations and is the cause of several clinical syndromes including respiratory disease, genital disease, and late-term abortions. Control of the virus in many parts of the world is achieved primarily through vaccination with either inactivated or modified-live viral vaccines. The purpose of this meta-analysis was to determine the cumulative efficacy of BoHV-1 vaccination to prevent abortion in pregnant cattle. Germane articles for inclusion in the analysis were identified through four online scientific databases and the examination of three review and ten primary study article reference lists. A total of 15 studies in 10 manuscripts involving over 7500 animals were included in the meta-analysis. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of vaccination. Subgroup analyses were performed based on type of vaccine, MLV or inactivated, and the type of disease challenge, experimentally induced compared to field studies. A 60% decrease in abortion risk in vaccinated cattle was demonstrated. The greatest decrease in abortion risk was seen in studies with intentional viral challenge although vaccination also decreased abortion risk in field studies. Both inactivated and modified-live viral vaccines decreased abortion risk. This meta-analysis provides quantitative support for the benefit of bovine herpesvirus 1 vaccination in the prevention of abortion. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of a tetanus toxoid marker to allow differentiation of infected from vaccinated poultry without affecting the efficacy of a H5N1 avian influenza virus vaccine.

PubMed

James-Berry, C M; Middleton, D; Mansfield, J P; Fenwick, S G; Ellis, T M

2010-10-30

Tetanus toxoid (TT) was assessed as a positive marker for avian influenza (AI) virus vaccination in chickens, in a vaccination and challenge study. Chickens were vaccinated twice with inactivated AI H5N2 virus vaccine, and then challenged three weeks later with highly pathogenic AI H5N1 virus. Vaccinated chickens were compared with other groups that were either sham-vaccinated or vaccinated with virus with the TT marker. All sham-vaccinated chickens died by 36 hours postinfection, whereas all vaccinated chickens, with or without the TT marker, were protected from morbidity and mortality following exposure to the challenge virus. Serological testing for H5-specific antibodies identified anamnestic responses to H5 in some of the vaccinated birds, indicating active virus infection.

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013–2014 in the United States

PubMed Central

Gaglani, Manjusha; Pruszynski, Jessica; Murthy, Kempapura; Clipper, Lydia; Robertson, Anne; Reis, Michael; Chung, Jessie R.; Piedra, Pedro A.; Avadhanula, Vasanthi; Nowalk, Mary Patricia; Zimmerman, Richard K.; Jackson, Michael L.; Jackson, Lisa A.; Petrie, Joshua G.; Ohmit, Suzanne E.; Monto, Arnold S.; McLean, Huong Q.; Belongia, Edward A.; Fry, Alicia M.; Flannery, Brendan

2016-01-01

Background. The predominant strain during the 2013–2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. Methods. The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2–17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. Results. We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR–confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%–61%). Among fully vaccinated children aged 2–17 years, the effectiveness of LAIV4 was 17% (95% CI, −39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%–74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. Conclusions. During 2013–2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States. PMID:26743842

Vaccination with a modified-live bovine viral diarrhea virus (BVDV) type 1a vaccine completely protected calves against challenge with BVDV type 1b strains.

PubMed

Xue, Wenzhi; Mattick, Debra; Smith, Linda; Umbaugh, Jerry; Trigo, Emilio

2010-12-10

Vaccination plays a significant role in the control of bovine viral diarrhea virus (BVDV) infection and spread. Recent studies revealed that type 1b is the predominant BVDV type 1 subgenotype, representing more than 75% of field isolates of BVDV-1. However, nearly all current, commercially available BVDV type 1 vaccines contain BVDV-1a strains. Previous studies have indicated that anti-BVDV sera, induced by BVDV-1a viruses, show less neutralization activity to BVDV-1b isolates than type 1a. Therefore, it is critically important to evaluate BVDV-1a vaccines in their ability to prevent BVDV-1b infection in calves. In current studies, calves were vaccinated subcutaneously, intradermally or intranasally with a single dose of a multivalent, modified-live viral vaccine containing a BVDV-1a strain, and were challenged with differing BVDV-1b strains to determine the efficacy and duration of immunity of the vaccine against these heterologous virus strains. Vaccinated calves, in all administration routes, were protected from respiratory disease caused by the BVDV-1b viruses, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding and greater white blood cell counts than non-vaccinated control animals. The BVDV-1a vaccine elicited efficacious protection in calves against each BVDV-1b challenge strain, with a duration of immunity of at least 6 months. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparative cost-effectiveness of HPV vaccines in the prevention of cervical cancer in Malaysia.

PubMed

Ezat, Sharifa W P; Aljunid, Syed

2010-01-01

Cervical cancer (CC) had the second highest incidence of female cancers in Malaysia in 2003-2006. Prevention is possible by both Pap smear screening and HPV vaccination with either the bivalent vaccine (BV) or the quadrivalent vaccine (QV). In the present study, cost effectiveness options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination). A scenario based sensitivity analysis was conducted using screening population coverages (40-80%) and costs of vaccines (RM 100-200/dose) were calculated. This was an economic burden, cross sectional study in 2006-2009 of respondents interviewed from six public Gynecology-Oncology hospitals. Methods included expert panel discussions to estimate treatment costs of CC, genital warts and vulva/vagina cancers by severity and direct interviews with respondents using costing and SF-36 quality of life questionnaires. A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear in the base case was RM 1,215 and RM 1,100 at increased screening coverage. With QV only, in base case it was RM 15,662 and RM 24,203 when the vaccination price was increased. With BV only, the respective figures were RM 1,359,057 and RM 2,530,018. For QV combined strategy cost/QALY in the base case it was RM 4,937, reducing to RM 3,395 in the best case and rising to RM 7,992 in the worst case scenario. With the BV combined strategy, these three cost/QALYs were RM 6,624, RM 4,033 and RM 10,543. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher was highly cost effective at RM 946.74 per QALYs saved but this was preceded by best case combined strategy with QV at RM 515.29 per QALYs saved. QV is more cost effective than BV. The QV combined strategy had a higher CE than

Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated Staphylococcal Poly-N-acetyl-beta-(1-6)-glucosamine.

PubMed

Maira-Litrán, Tomás; Kropec, Andrea; Goldmann, Donald A; Pier, Gerald B

2005-10-01

Staphylococcus aureus and Staphylococcus epidermidis both synthesize the surface polysaccharide poly-N-acetyl-beta-(1-6)-glucosamine (PNAG), which is produced in vitro with a high level (>90%) of the amino groups substituted by acetate. Here, we examined the role of the acetate substituents of PNAG in generating opsonic and protective antibodies. PNAG and a deacetylated form of the antigen (dPNAG; 15% acetylation) were conjugated to the carrier protein diphtheria toxoid (DT) and used to immunize animals. Mice responded in a dose-dependent fashion to both conjugate vaccines, with maximum antibody titers observed at the highest dose and 4 weeks after the last of three weekly immunizations. PNAG-DT and dPNAG-DT vaccines were also very immunogenic in rabbits. Antibodies raised to the conjugate vaccines in rabbits mediated the opsonic killing of various staphylococcal strains, but the specificity of the opsonic killing was primarily to dPNAG, as this antigen inhibited the killing of S. aureus strains by both PNAG- and dPNAG-specific antibodies. Passive immunization of mice with anti-dPNAG-DT rabbit sera showed significant levels of clearance of S. aureus from the blood (54 to 91%) compared to control mice immunized with normal rabbit sera, whereas PNAG-specific antibodies were ineffective at clearing S. aureus. Passive immunization of mice with a goat antiserum raised to the dPNAG-DT vaccine protected against a lethal dose of three different S. aureus strains. Overall, these data show that immunization of animals with a conjugate vaccine of dPNAG elicit antibodies that mediated opsonic killing and protected against S. aureus infection, including capsular polysaccharide types 5 and 8 and an untypable strain.

Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza vaccines in adults: results of a randomized, controlled trial.

PubMed

Scheifele, David W; Ward, Brian J; Dionne, Marc; Vanderkooi, Otto G; Loeb, Mark; Coleman, Brenda L; Li, Yan

2012-07-06

When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but compatibility of the two had not been assessed. To compare responses after concurrent or sequential administration of these vaccines, adults 20-59 years old were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur, Toronto) given concurrently or 21 days later. Blood was obtained at baseline and 21 days after each vaccination to measure hemagglutination inhibition (HAI) titers. Adverse effects were assessed using symptom diaries and personal interviews. 282 participants completed the study (concurrent vaccines 145, sequential vaccines 137). HAI titers to H1N1pdm09 were ≥ 40 at baseline in 15-18% of participants and following vaccination in 91-92%. Initially seropositive subjects (titer ≥ 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded GM responses of initially naïve participants, which were unaffected by concurrent TIV. Responses to TIV were not lower after concurrent than separate vaccination. Adverse event rates were not increased by concurrent vaccinations above those with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic and compatible with concurrently administered TIV. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study

PubMed Central

Dimitrov, Dobromir T.; Troeger, Christopher; Halloran, M. Elizabeth; Longini, Ira M.; Chao, Dennis L.

2014-01-01

Background Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. Methods & Findings We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. Conclusions We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions. PMID:25473851

Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination

PubMed Central

Thebault, Simon; Waters, Patrick; Snape, Matthew D.; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J.; Vincent, Angela

2015-01-01

Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients’ CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research. PMID:26090827

Neuronal Antibodies in Children with or without Narcolepsy following H1N1-AS03 Vaccination.

PubMed

Thebault, Simon; Waters, Patrick; Snape, Matthew D; Cottrell, Dominic; Darin, Niklas; Hallböök, Tove; Huutoniemi, Anne; Partinen, Markku; Pollard, Andrew J; Vincent, Angela

2015-01-01

Type 1 narcolepsy is caused by deficiency of hypothalamic orexin/hypocretin. An autoimmune basis is suspected, but no specific antibodies, either causative or as biomarkers, have been identified. However, the AS03 adjuvanted split virion H1N1 (H1N1-AS03) vaccine, created to protect against the 2009 Pandemic, has been implicated as a trigger of narcolepsy particularly in children. Sera and CSFs from 13 H1N1-AS03-vaccinated patients (12 children, 1 young adult) with type 1 narcolepsy were tested for autoantibodies to known neuronal antigens including the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein 2 (CASPR2), both associated with encephalopathies that include disordered sleep, to rodent brain tissue including the lateral hypothalamus, and to live hippocampal neurons in culture. When sufficient sample was available, CSF levels of melanin-concentrating hormone (MCH) were measured. Sera from 44 H1N1-ASO3-vaccinated children without narcolepsy were also examined. None of these patients' CSFs or sera was positive for NMDAR or CASPR2 antibodies or binding to neurons; 4/13 sera bound to orexin-neurons in rat brain tissue, but also to other neurons. MCH levels were a marginally raised (n = 8; p = 0.054) in orexin-deficient narcolepsy patients compared with orexin-normal children (n = 6). In the 44 H1N1-AS03-vaccinated healthy children, there was no rise in total IgG levels or in CASPR2 or NMDAR antibodies three weeks following vaccination. In conclusion, there were no narcolepsy-specific autoantibodies identified in type 1 narcolepsy sera or CSFs, and no evidence for a general increase in immune reactivity following H1N1-AS03 vaccination in the healthy children. Antibodies to other neuronal specific membrane targets, with their potential for directing use of immunotherapies, are still an important goal for future research.

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

PubMed

Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

2016-09-01

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

PubMed Central

Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

2012-01-01

Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

Efficacy of intranasal vaccination with a multivalent vaccine containing temperature-sensitive modified-live bovine herpesvirus type 1 for protection of seronegative and seropositive calves against respiratory disease.

PubMed

Mahan, Suman M; Sobecki, Brian; Johnson, John; Oien, Nancee L; Meinert, Todd R; Verhelle, Sarah; Mattern, Sally J; Bowersock, Terry L; Leyh, Randy D

2016-06-01

OBJECTIVE To evaluate efficacy and duration of immunity of the bovine herpesvirus type 1 (BHV-1) fraction of a trivalent vaccine also containing parainfluenza virus-3 and bovine respiratory syncytial virus fractions administered intranasally (IN) for protection of calves against infectious bovine rhinotracheitis (IBR). DESIGN Controlled challenge study. ANIMALS 120 dairy calves (3 to 8 days old) seronegative for antibody against BHV-1 (experiments 1 and 2) or seropositive for maternally derived antibody against BHV-1 (experiment 3). PROCEDURES In 3 separate experiments, calves were vaccinated IN via 2 nostrils (experiment 1) or 1 nostril (experiments 2 and 3) with a vaccine containing or not containing a BHV-1 fraction. For seronegative calves, the test vaccine contained a minimum immunizing dose of BHV-1; for seropositive calves, it contained a commercial dose of BHV-1. Calves were challenged IN with virulent BHV-1 on day 28 or 193 (seronegative calves) or day 105 (seropositive calves) after vaccination to evaluate vaccine efficacy. Frequency and duration of clinical signs, rectal temperatures, virus shedding, and serologic responses were compared between treatment groups within experiments. RESULTS In all experiments, BHV-1 vaccinated calves had lower frequencies or shorter durations of clinical signs of IBR than did control calves. Following viral challenge, peak rectal temperatures and degrees of virus shedding were lower and serologic responses were higher in vaccinated versus control calves. CONCLUSIONS AND CLINICAL RELEVANCE IN vaccination against BHV-1 protected all calves against clinical IBR disease, regardless of serologic status at the time of vaccination, and suppressed virus shedding. A single dose of this IN vaccine has the potential to protect seronegative calves for at least 193 days and override maternally derived antibody to protect seropositive calves for at least 105 days.

Seroprevalence of influenza A H1N1 and seroconversion of mothers and infants induced by a single dose of monovalent vaccine.

PubMed

Chao, Anne; Huang, Yhu-Chering; Chang, Yao-Lung; Wang, Tzu-Hao; Chang, Shuenn-Dyh; Wu, Ting-Shu; Wu, Tsu-Lan; Chao, An-Shine

2013-09-01

To determine the prevalence of preexisting antibodies against the pandemic 2009 Influenza A (H1N1) virus in pregnant women and to evaluate the seroprotection of the mothers and infants by a single injection of monovalent vaccine during the pandemic. Seropositivity rate of H1N1 among the nonvaccinated were compared with the vaccinated women. A single dose of vaccine, either nonadjuvanted AdimFlu-S or MF59-adjuvanted vaccine, was injected to the voluntarily vaccinated group. Maternal and cord blood sera were collected to evaluate the antibody response of the H1N1 virus. Seropositivity was defined as a hemagglutination inhibition titer to H1N1 (A/Taiwan/126/09) ≥ 1:40. A total of 210 healthy, singleton, pregnant women were enrolled between January 2010 and May 2010. Seropositivity (≥ 1:40) of maternal hemagglutination inhibition was significantly higher in the vaccinated group (78%) than the nonvaccinated group (9.5%); 41.6% (20/48) of seropositive titers were >1:80. In nine vaccinated cases resulting in negative serum titers (<1:40), the prevalence of negative titer in the women received AdimFlu-S (14.8%, 4/31) was lower (p = 0.025) than those received MF59-adjuvanted vaccine (50%, 5/10). Subclinical infection against H1N1 was low in Taiwanese pregnant women in the pandemic 2009. Seropositivity >75% could be achieved in the paired maternal and cord serum samples by a single injection of monovalent H1N1 vaccine. Copyright © 2013. Published by Elsevier B.V.

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.

[Post-exposure antirabies vaccination. Early serological response to vaccine cultivated on VERO cells using a reduced 2-1-1 schedule].

PubMed

Colnot, F; Sureau, P; Alexandre, J L; Arnaudo, J P; Hesse, J Y; Jeanmaire, H

1994-11-12

An abbreviated 2-1-1 schedule for post-exposure rabies vaccination would theoretically lead to more rapid production of specific antibodies than the classical schedule. We measured early serological response to the 2-1-1 schedule. Patients consulting the antirabies centre of the Epinal hospital from June 1992 to June 1993 who had never been vaccinated and whose exposure history justified antirabies vaccination were included in this study. Fifty subjects were vaccinated with PVRV (purified vero rabies vaccine, Pasteur Institute) cultured on VERO (vervet monkey origin) cells using the abbreviated 2-1-1 schedule of 2 doses (0.5 ml = 2.5 IU/dose) on day 0 and 1 dose on days 7 and 21. Antirabies antibodies were assayed using the Platelia Rage immunoenzyme method (Diagnostic Pasteur) on day 21. Titres above 0.5 IU were considered to give protection and non-protected subjects were seen again on day 28 for a supplementary dose. Only 34 subjects (68%) had protective antibody titres on day 21, but by day 28, 48 (96%) had acquired immunity. In this study population, the age range was from 1 to 83 years and age over 30 years appeared to delay antibody formation. These findings emphasize the importance of initial antirabies immunoglobulins if short incubation in suspected and the need for serological follow-up if delayed antibody formation is suspected (subjects over 30).

Addressing the Vaccine Hesitancy Continuum: An Audience Segmentation Analysis of American Adults Who Did Not Receive the 2009 H1N1 Vaccine

PubMed Central

Ramanadhan, Shoba; Galarce, Ezequiel; Xuan, Ziming; Alexander-Molloy, Jaclyn; Viswanath, Kasisomayajula

2015-01-01

Understanding the heterogeneity of groups along the vaccine hesitancy continuum presents an opportunity to tailor and increase the impact of public engagement efforts with these groups. Audience segmentation can support these goals, as demonstrated here in the context of the 2009 H1N1 vaccine. In March 2010, we surveyed 1569 respondents, drawn from a nationally representative sample of American adults, with oversampling of racial/ethnic minorities and persons living below the United States Federal Poverty Level. Guided by the Structural Influence Model, we assessed knowledge, attitudes, and behaviors related to H1N1; communication outcomes; and social determinants. Among those who did not receive the vaccine (n = 1166), cluster analysis identified three vaccine-hesitant subgroups. Disengaged Skeptics (67%) were furthest from vaccine acceptance, with low levels of concern and engagement. The Informed Unconvinced (19%) were sophisticated consumers of media and health information who may not have been reached with information to motivate vaccination. The Open to Persuasion cluster (14%) had the highest levels of concern and motivation and may have required engagement about vaccination broadly. There were significant sociodemographic differences between groups. This analysis highlights the potential to use segmentation techniques to identify subgroups on the vaccine hesitancy continuum and tailor public engagement efforts accordingly. PMID:26350595

Immunogenicity and sustainability of the immune response in Brazilian HIV-1-infected individuals vaccinated with inactivated triple influenza vaccine.

PubMed

Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B

2016-03-01

HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination. © 2015 Wiley Periodicals, Inc.

Vaccinating my way--use of alternative vaccination schedules in New York State.

PubMed

Nadeau, Jessica A; Bednarczyk, Robert A; Masawi, Munyaradzi R; Meldrum, Megan D; Santilli, Loretta; Zansky, Shelley M; Blog, Debra S; Birkhead, Guthrie S; McNutt, Louise-Anne

2015-01-01

To identify children vaccinated following an alternative vaccine schedule using immunization information system data and determine the impact of alternative schedule use on vaccine coverage. Children born in New York State, outside New York City, between January 1, 2009 and August 14, 2011 were assessed for vaccination patterns consistent with use of an alternative schedule. Children who by 9 months of age had at least 3 vaccination visits recorded in the statewide mandatory immunization information system after 41 days of age were classified as either attempting to conform to the Centers for Disease Control and Prevention published recommended vaccination schedule or an alternative schedule. The number of vaccination visits and up-to-date status at age 9 months were compared between groups. Of the 222 628 children studied, the proportion of children following an alternative schedule was 25%. These children were significantly less likely to be up-to-date at age 9 months (15%) compared with those conforming to the routine schedule (90%, P < .05). Children following an alternative schedule on average had about 2 extra vaccine visits compared with children following a routine schedule (P < .05). Almost 1 in 4 children in this study appear to be intentionally deviating from the routine schedule. Intentional deviation leads to poor vaccination coverage leaving children vulnerable to infection and increasing the potential for vaccine-preventable disease outbreaks. Copyright © 2015 Elsevier Inc. All rights reserved.

AF03-adjuvanted and non-adjuvanted pandemic influenza A (H1N1) 2009 vaccines induce strong antibody responses in seasonal influenza vaccine-primed and unprimed mice.

PubMed

Caillet, Catherine; Piras, Fabienne; Bernard, Marie-Clotilde; de Montfort, Aymeric; Boudet, Florence; Vogel, Frederick R; Hoffenbach, Agnès; Moste, Catherine; Kusters, Inca

2010-04-19

Pandemic influenza vaccines have been manufactured using the A/California/07/2009 (H1N1) strain as recommended by the World Health Organization. We evaluated in mice the immunogenicity of pandemic (H1N1) 2009 vaccine and the impact of prior vaccination against seasonal trivalent influenza vaccines (TIV) on antibody responses against pandemic (H1N1) 2009. In naïve mice, a single dose of unadjuvanted H1N1 vaccine (3 microg of HA) was shown to elicit hemagglutination inhibition (HI) antibody titers >40, a titer associated with protection in humans against seasonal influenza. A second vaccine dose of pandemic (H1N1) 2009 vaccine strongly increased these titers, which were consistently higher in mice previously primed with TIV than in naïve mice. At a low immunization dose (0.3 microg of HA), the AF03-adjuvanted vaccine elicited higher HI antibody titers than the corresponding unadjuvanted vaccines in both naïve and TIV-primed animals, suggesting a potential for antigen dose-sparing. These results are in accordance with the use in humans of a split-virion inactivated pandemic (H1N1) 2009 vaccine formulated with or without AF03 adjuvant to protect children and young adults against influenza A (H1N1) 2009 infection. Copyright 2010 Elsevier Ltd. All rights reserved.

Differentiation of BHV-1 isolates from vaccine virus by high-resolution melting analysis.

PubMed

Ostertag-Hill, Claire; Fang, Liang; Izume, Satoko; Lee, Megan; Reed, Aimee; Jin, Ling

2015-02-16

An efficacious bovine herpesvirus type-1 (BHV-1) vaccine has been used for many years. However, in the past few years, abortion and respiratory diseases have occurred after administration of the modified live vaccine. To investigate whether BHV-1 isolates from disease outbreaks are identical to those of the vaccines used, selected regions of the BHV-1 genome were investigated by high-resolution melting (HRM) analysis and PCR-DNA sequencing. When a target region within the thymidine kinase (TK) gene was examined by HRM analysis, 6 out of the 11 isolates from abortion cases and 22 out of the 25 isolates from bovine respiratory disease (BRD) cases had different melting curves compared to the vaccine virus. Surprisingly, when a conserved region within the US6 gene that encodes glycoprotein D (gD) was examined by HRM analysis, 5 out of the 11 abortion isolates and 18 out of the 23 BRD isolates had different melting curves from the vaccine virus. To determine whether SNPs within the coding regions of glycoprotein E (gE) and TK genes can be used to differentiate the isolates from the vaccine virus, PCR-DNA sequencing was used to examine these SNPs in all the isolates. This revealed that only 1 out of 11 of the abortion isolates and 4 out of 24 of the BRD isolates are different in the target region of gE from the vaccine virus, while 5 out of 11 abortion isolates and 4 out of 22 BRD isolates are different in the target region of TK from the vaccine virus. No DNA sequence differences were observed in glycoprotein G (gG) region between disease and vaccine isolates. Our study demonstrated that many disease isolates had genetic differences from the vaccine virus in regions examined by HRM and PCR-DNA sequencing analysis. In addition, many isolates contained more than one type of mutation and were composed of mixed variants. Our study suggests that a mixture of variants were present in isolates collected post-vaccination. HRM is a rapid diagnostic method that can be used for

Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

PubMed Central

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

Yeast Surface-Displayed H5N1 Avian Influenza Vaccines

PubMed Central

Lei, Han; Jin, Sha; Karlsson, Erik; Schultz-Cherry, Stacey

2016-01-01

Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation. PMID:28078309

Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

PubMed Central

Libster, Romina; McNeal, Monica; Walter, Emmanuel B.; Shane, Andi L.; Winokur, Patricia; Cress, Gretchen; Berry, Andrea A.; Kotloff, Karen L.; Sarpong, Kwabena; Turley, Christine B.; Harrison, Christopher J.; Pahud, Barbara A.; Marbin, Jyothi; Dunn, John; El-Khorazaty, Jill; Barrett, Jill

2016-01-01

BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6–14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A ≥20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. PMID:26823540

Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

PubMed Central

Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

2017-01-01

Abstract Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection. PMID:28535276

Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination

PubMed Central

Miura, Kazutoyo; Zhou, Hong; Moretz, Samuel E.; Diouf, Ababacar; Thera, Mahamadou A; Dolo, Amagana; Doumbo, Ogobara; Malkin, Elissa; Diemert, David; Miller, Louis H.; Mullen, Gregory E.D.; Long, Carole A.

2009-01-01

Vaccines represent a significant potential means of decreasing global morbidity and mortality due to malaria. Clinical trials in the U.S. with Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) showed that the vaccine induced biologically active antibodies judged by an in vitro parasite Growth Inhibition Assay (GIA). However, the same vaccine in Malian adults did not increase biological activity although it elevated ELISA titers. As GIA has been used to evaluate the biological activity of antibodies induced by blood-stage malarial vaccine candidates, we explored this discrepancy in this study. We affinity purified AMA1-specific antibodies from both US vaccinees and from non-vaccinated individuals living in a malaria-endemic area of Mali, and performed ELISA and GIA. Both AMA1-specifc antibodies induced by vaccination (US) and by natural infection (Mali) have comparable biological activity in GIA when the ELISA titer is normalized. However, a fraction of Malians’ IgG which did not bind to AMA1 protein (Mali-non-AMA1 IgG) reduced the biological activity of the AMA1 antibodies from US vaccinees; in contrast, US-non-AMA1 IgGs did not show a reduction of the biological activity. Further investigation revealed that the reduction was due to malaria-specific IgGs in the Mali-non-AMA1 IgGs. The fact that both US- and Mali-AMA1-specific antibodies showed comparable biological activity supports further development of AMA1-based vaccines. However, the reduction of biological activity of AMA1-specific antibody by other malaria-specific IgGs likely explains the limited effect on growth-inhibitory activity of antibodies induced by AMA1 vaccination in Malian adults and may complicate efforts to develop a blood-stage malaria vaccine. PMID:19050299

Adverse events in vaccinations for travelers - a 1-year prospective survey in a travel clinic in Germany.

PubMed

Slesak, Günther; Fleck, Ralf; Scherbaum, Helmut; Blumenstock, Gunnar; Schäfer, Johannes

2018-01-01

The study goal was to assess and compare adverse events (AE) of current vaccinations for travelers under 'real-life conditions'. A prospective observational online questionnaire study was performed from May 2015 till April 2016 in a travel clinic in Germany. Online questionnaire links were sent 1 week after the first vaccination date. Severity was rated on a scale from 1 to 5 (minor to very severe AE). Of 1357 vaccinees 781 (57.6%) responded to the questionnaire, corresponding to 1415 vaccinations (1-7 simultaneous vaccinations). Responders were more often female (f:m = 1.29:1). Main age groups were 20-29 years old (36.1%). Most frequent vaccinations were against rabies (277; chick embryo cell vaccine (CEC): 97, human diploid cell vaccine (HDC): 180), yellow fever (250), typhoid fever (198), meningococcal meningitis (126) and Japanese encephalitis (104). A total of 217 vaccinees (27.8%) reported AE; 82 (10.5%) rated AE as more severe (grade 3: 61, grade 4: 18, grade 5: 3). No life-threatening AE was reported. Of 157 systemic AE the most frequent were: fatigue (75), headaches (46) and pyrexia (31). Of 94 local AE most frequently reported were pain (66), myalgia (25) and swelling (12). AE after single vaccinations were more often associated with rabies vaccine (OR 2.2; 1.2-4.2). AE increased with the number of simultaneous vaccinations (single vaccination: 24.1%, 88/365; 2 vaccinations: 26.6%, 73/274, ≥3 vaccinations: 39.4%, 56/142, χ2 = 12.24, P = 0.002, CCorr = 0.18), but more severe AE showed no association with the number of vaccinations (χ2 = 5.55, P = 0.06, CCorr = 0.12). Single and simultaneous vaccinations were overall well tolerated. AE were reported more frequently with rabies vaccinations in single vaccinations. Increased numbers of simultaneous vaccinations led to some incremental AE but not to more severe AE. Simultaneous vaccinations should be encouraged to reduce missed opportunities for immunizations.

Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study.

PubMed

Fisker, Ane B; Hornshøj, Linda; Rodrigues, Amabelia; Balde, Ibraima; Fernandes, Manuel; Benn, Christine S; Aaby, Peter

2014-08-01

In 2008, the GAVI Alliance funded the introduction of new vaccines (including pentavalent diphtheria-tetanus-pertussis [DTP] plus hepatitis B and Haemophilus influenzae type b antigens) in Guinea-Bissau. The introduction was accompanied by increased vaccination outreach services and a more restrictive wastage policy, including only vaccinating children younger than 12 months. We assessed coverage of all vaccines in the Expanded Program on Immunizations before and after the new vaccines' introduction, and the implications on child survival. This observational cohort study used data from the Bandim Health Project, which has monitored vaccination status and mortality in randomly selected village clusters in Guinea-Bissau since 1990. We assessed the change in vaccination coverage using cohort data from children born in 2007 and 2009; analysed the proportion of children who received measles vaccine after 12 months of age using data from 1999-2006; and compared child mortality after age 12 months in children who had received measles vaccine and those who had not using data from 1999 to 2006. The proportion of children who were fully vaccinated by 12 months of age was 53% (468 of 878) in the 2007 cohort and 53% (467 of 879) in the 2009 cohort (relative risk [RR] 1·00, 95% CI 0·89-1·11). Coverage of DTP-3 and pentavalent-3 increased from 73% (644 of 878) in 2007 to 81% (712 of 879) in 2009 (RR 1·10, 95% CI 1·04 -1·17); by contrast, the coverage of measles vaccination declined from 71% (620 of 878) to 66% (577 of 879; RR 0·93, 0·85-1·01). The effect of the changes was significantly different for DTP-3 coverage compared with measles vaccine coverage (p=0·002). After 12 months of age, the adjusted mortality rate ratio was 0·71 (95% CI 0·56-0·90) for children who had received measles vaccine compared with those who had not (0·59 [0·43-0·80] for girls and 0·87 [0·62-1·23] for boys). The introduction of the new vaccination programme in 2008 was associated with

Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States.

PubMed

Caspard, Herve; Coelingh, Kathleen L; Mallory, Raburn M; Ambrose, Christopher S

2016-09-30

This analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013-2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013-2014. Post hoc analyses of a 2013-2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009-2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location. From the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P<0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors' central locations. The review of LAIV VE studies showed that in the 2010-2011 and 2013-2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010-2014. This study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility

[Pandemic influenza A (H1N1)v vaccination status and factors affecting vaccination: Ankara and Diyarbakır 2009 data from Turkey].

PubMed

Ertek, Mustafa; Sevencan, Funda; Kalaycıoğlu, Handan; Gözalan, Ayşegül; Simşek, Ciğdem; Culha, Gönül; Dorman, Vedat; Ozlü, Ahmet; Arıkan, Füsun; Aktaş, Dilber; Akın, Levent; Korukluoğlu, Gülay; Sevindi, Demet Furkan

2011-10-01

In this study, it was aimed to determine the frequency of the symptoms of influenza-like illness during influenza A (H1N1)v pandemic in two provinces where sentinel influenza surveillance was conducted and also to obtain opinions about H1N1 influenza and vaccination, H1N1 vaccination status and factors affecting vaccination. This cross-sectional study was conducted in the provinces of Ankara (capital city, located at Central Anatolia) and Diyarbakır (located at southeastern Anatolia). It was planned to include 455 houses in Ankara and 276 houses in Diyarbakır. The household participation rate in the study was 78.9% and 53.6% for Ankara and Diyarbakır, respectively. Our study was carried out between January-February 2010, with 1164 participants from Ankara and 804 from Diyarbakır, including every household subjects except for infants younger than 11 months and patients with primary/secondary immunodeficiency diseases. Data was collected by site teams consisting of a physician and a healthcare staff with informed consent. Of the participants 45.5% from Ankara and 35.3% from Diyarbakır stated that they had gone through an influenza-like illness. The most frequently indicated clinical symptoms were fatigue/weakness, rhinitis, sore throat and cough. The rates of admission to a physician with influenza like illness complaints were 50.6% and 58.7%; rates of hospitalization due to influenza-like illness were 1% and 1.5%, and rates of antiviral drug use were 3.8% and 1.9%, in Ankara ve Diyarbakır participants, respectively. The rate of personal precautions taken by the subjects for prevention from pandemic influenza were 59% and 53.3%, in Ankara and Diyarbakır, respectively. These precautions most frequently were "hand washing" and "avoiding crowded public areas". H1N1 influenza vaccine was applied in 9.3% of the participants in Ankara and in 3.7% of the participants in Diyarbakır. Vaccination rate was higher in both of the provinces in adults over 25 years old than

Comparative trial of the canine parvovirus, canine distemper virus and canine adenovirus type 2 fractions of two commercially available modified live vaccines.

PubMed

Bergman, J G H E; Muniz, M; Sutton, D; Fensome, R; Ling, F; Paul, G

2006-11-25

The results of vaccinating two groups of puppies with commercial vaccines, both of which claimed to provide adequate protection with a final vaccination at 10 weeks of age, were compared. Groups of 19 and 20 puppies with similar titres of maternally derived antibodies against canine parvovirus (cpv), canine distemper virus (cdv) and canine adenovirus type 2 (cav-2) at four weeks of age were vaccinated at six and 10 weeks of age and their responses to each vaccination were measured by comparing the titres against cpv, cdv and cav-2 in the serum samples taken immediately before the vaccination and four weeks later. After the vaccination at six weeks of age, all 19 of the puppies in group 1 had responded to cpv and cdv, and 14 had responded to cav-2; in group 2, 17 of the 20 had responded to cpv, 19 to cdv and 15 to cav-2. In both groups the puppies that did not respond to the first vaccination had responded serologically to cpv, cdv and cav-2 at 10 weeks of age.

Bovine herpesvirus 1 modified live virus vaccines for cattle reproduction: Balancing protection with undesired effects.

PubMed

Chase, Christopher C L; Fulton, Robert W; O'Toole, Donal; Gillette, Benjamin; Daly, Russell F; Perry, George; Clement, Travis

2017-07-01

Bovine herpesvirus 1 (BoHV-1) has long been associated with reproductive failure in cattle following infection of the ovary and/or fetus. Vaccination prior to breeding has been an effective approach to lessen the impact of BoHV-1 on reproduction. Prior studies in the 1980s and 1990s established the susceptibility of the ovary and particularly the corpus luteum (CL) to BoHV-1 infection. A series of studies at breeding time established that: (1) in naïve animals, the CL was the major target of BoHV-1 pathology; (2) CL lesions occurred within 4-9 days after estrus; (3) similar lesions was seen with BoHV-1 MLV vaccines; (4) ovarian lesions varied by the vaccine strain used; (5) progesterone decreased with or without CL lesions; and (6) following reactivation of BoHV-1 latent infection, ovaries could become reinfected in the face of BoHV-1 immunity. Large scale field studies demonstrated that conception was highest in animals previously vaccinated and boostered with inactivated vaccine compared to animals revaccinated with MLV. In the early 2000s, to get a label claim to vaccinate calves nursing pregnant cows, safety study outlines were approved by USDA-APHIS CVB. These studies were designed to determine the effect of revaccination with MLV during pregnancy on previously vaccinated cows and were not rigorous enough to confirm complete fetal safety. As designed these studies showed no difference in reproductive loss between the previously vaccinated animals and the animals revaccinated ∼4, 7 and 9 months later, leading to the label approval for MLV vaccination in pregnant cows. Subsequent investigations by diagnostic laboratories found an increase in BoHV-1 reproductive loss after the approval for use in pregnant animals. A method was developed to differentiate IBR vaccine strains from field strains. Analysis of viruses from 31 cases from 2009-2016 indicated that all 31 isolates matched with vaccine strains. Going forward, it will be necessary to develop vaccine

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

PubMed

Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

2014-08-21

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

Autoantibody response to adjuvant and nonadjuvant H1N1 vaccination in systemic lupus erythematosus.

PubMed

Urowitz, Murray B; Anton, Anoja; Ibanez, Dominique; Gladman, Dafna D

2011-11-01

It has been reported that influenza vaccination increases autoantibody production and/or disease activity in a significant proportion of patients with systemic lupus erythematosus (SLE). During the recent H1N1 epidemic, we investigated whether the use of adjuvant- and nonadjuvant-containing H1N1 vaccine induced increased autoantibody production in patients with SLE. Patients with SLE who received H1N1 vaccination and had a battery of 9 autoantibodies tested before and 1 and 3 months after vaccination were included. Antibodies tested included rheumatoid factor (nephelometry), antinuclear antibody (immunofluorescence), anti-DNA (Farr), anti-RNP, anti-Sm, anti-Ro, anti-La, anti-Scl-70, and anti-Jo-1 (enzyme-linked immunosorbent assay). Patients were evaluated by standard protocol, including items necessary to calculate the Systemic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Descriptive statistics and McNemar's test were performed to evaluate change in antibody positivity. Multivariate logistic regression was performed to adjust for repeated measures in the comparisons of autoantibodies over visits and vaccine types. One hundred three patients (94 women, 9 men) with a mean ± SD age at vaccination of 43.9 ± 15.2 years and a mean ± SD disease duration of 14.2 ± 11.0 years were included. Fifty-one patients received adjuvant and 52 received nonadjuvant vaccines. Antibody testing was performed a mean of 1.9 months prior to the vaccination. The first postvaccination sample was taken a mean of 1 month after vaccination and the second a mean of 3.5 months after vaccination. The percentage of patients with changes in antibodies following vaccination was not statistically significant for most antibodies. After adjusting for the number of tests performed, none of the associations was significant. H1N1 vaccination (both adjuvant and nonadjuvant) did not increase the

Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

PubMed

Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

2015-06-01

Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care.

PubMed

Pierce, Jennifer Young; Korte, Jeffrey E; Carr, Laura A; Gasper, Catherine B; Modesitt, Susan C

2013-07-17

Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11-12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11-12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child's vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, 95% CI 0.61-0.85 and RR 0.85, 95% CI 0.72-1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort.

New approaches to design HIV-1 T-cell vaccines.

PubMed

Perrin, Hélène; Canderan, Glenda; Sékaly, Rafick-Pierre; Trautmann, Lydie

2010-09-01

Following the evidence that T-cell responses are crucial in the control of HIV-1 infection, vaccines targeting T-cell responses were tested in recent clinical trials. However, these vaccines showed a lack of efficacy. This review attempts to define the qualitative and quantitative features that are desirable for T-cell-induced responses by vaccines. We also describe strategies that could lead to achievement of this goal. Using the yellow fever vaccine as a benchmark of an efficient vaccine, recent studies identified factors of immune protection and more importantly innate immune pathways needed for the establishment of long-term protective adaptive immunity. To prevent or control HIV-1 infection, a vaccine must induce efficient and persistent antigen-specific T cells endowed with mucosal homing capacity. Such cells should have the capability to counteract HIV-1 diversity and its rapid spread from the initial site of infection. To achieve this goal, the activation of a diversified innate immune response is critical. New systems biology approaches will provide more precise correlates of immune protection that will pave the way for new approaches in T-cell-based vaccines.

Seasonal Influenza Vaccine and Protection against Pandemic (H1N1) 2009-Associated Illness among US Military Personnel

PubMed Central

Johns, Matthew C.; Eick, Angelia A.; Blazes, David L.; Lee, Seung-eun; Perdue, Christopher L.; Lipnick, Robert; Vest, Kelly G.; Russell, Kevin L.; DeFraites, Robert F.; Sanchez, Jose L.

2010-01-01

Introduction A novel A/H1N1 virus is the cause of the present influenza pandemic; vaccination is a key countermeasure, however, few data assessing prior seasonal vaccine effectiveness (VE) against the pandemic strain of H1N1 (pH1N1) virus are available. Materials and Methods Surveillance of influenza-related medical encounter data of active duty military service members stationed in the United States during the period of April–October 2009 with comparison of pH1N1-confirmed cases and location and date-matched controls. Crude odds ratios (OR) and VE estimates for immunized versus non-immunized were calculated as well as adjusted OR (AOR) controlling for sex, age group, and history of prior influenza vaccination. Separate stratified VE analyses by vaccine type (trivalent inactivated [TIV] or live attenuated [LAIV]), age groups and hospitalization status were also performed. For the period of April 20 to October 15, 2009, a total of 1,205 cases of pH1N1-confirmed cases were reported, 966 (80%) among males and over one-half (58%) under 25 years of age. Overall VE for service members was found to be 45% (95% CI, 33 to 55%). Immunization with prior season's TIV (VE = 44%, 95% CI, 32 to 54%) as well as LAIV (VE = 24%, 95% CI, 6 to 38%) were both found to be associated with protection. Of significance, VE against a severe disease outcome was higher (VE = 62%, 95% CI, 14 to 84%) than against milder outcomes (VE = 42%, 95% CI, 29 to 53%). Conclusion A moderate association with protection against clinically apparent, laboratory-confirmed Pandemic (H1N1) 2009-associated illness was found for immunization with either TIV or LAIV 2008–09 seasonal influenza vaccines. This association with protection was found to be especially apparent for severe disease as compared to milder outcome, as well as in the youngest and older populations. Prior vaccination with seasonal influenza vaccines in 2004–08 was also independently associated with protection. PMID:20502705

Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals.

PubMed

Sun, Peifang; Crum-Cianflone, Nancy F; Defang, Gabriel; Williams, Maya; Ganesan, Anuradha; Agan, Brian K; Lalani, Tahaniyat; Whitman, Timothy; Brandt, Carolyn; Burgess, Timothy H

2017-10-27

This study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV + and HIV - groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine. Blood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG + memory B cells (B Mem ) and IFNγ + T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively. Overall B Mem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific B Mem at day 28 for the HIV - /LAIV, HIV - /TIV and HIV + /TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of B Mem between HIV - /LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/10 6 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold. Participants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV + and HIV - subject groups in terms of B Mem . The B Mem response declined at 6months. Copyright © 2017. Published by Elsevier Ltd.

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study.

PubMed

Treanor, John T; Albano, Frank R; Sawlwin, Daphne C; Graves Jones, Alison; Airey, Jolanta; Formica, Neil; Matassa, Vince; Leong, Jane

2017-04-04

Vaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014-2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18years. Participants (n=3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n=1741), IIV3-YAM (n=871), or IIV3-VIC (n=872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI]≤1.5) and seroconversion rate (SCR) difference (IIV3 - IIV4; upper bound of two-sided 95% CI≤10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination. IIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were -1.1 (-4.5, 2.3), -1.7 (-5.0, 1.7), -3.2 (IIV3-YAM; -7.4, 0.9), and -1.6 (IIV3-VIC; -5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%). IIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains

AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice

PubMed Central

Yam, Karen K.; Gupta, Jyotsana; Winter, Kaitlin; Allen, Elizabeth; Brewer, Angela; Beaulieu, Édith; Mallett, Corey P.; Burt, David S.; Ward, Brian J.

2015-01-01

During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies. PMID:25972874

The Effect of Vaccination on the Evolution and Population Dynamics of Avian Paramyxovirus-1

PubMed Central

Hudson, Peter J.; Poss, Mary

2010-01-01

Newcastle Disease Virus (NDV) is a pathogenic strain of avian paramyxovirus (aPMV-1) that is among the most serious of disease threats to the poultry industry worldwide. Viral diversity is high in aPMV-1; eight genotypes are recognized based on phylogenetic reconstruction of gene sequences. Modified live vaccines have been developed to decrease the economic losses caused by this virus. Vaccines derived from avirulent genotype II strains were developed in the 1950s and are in use globally, whereas Australian strains belonging to genotype I were developed as vaccines in the 1970s and are used mainly in Asia. In this study, we evaluated the consequences of attenuated live virus vaccination on the evolution of aPMV-1 genotypes. There was phylogenetic incongruence among trees based on individual genes and complete coding region of 54 full length aPMV-1 genomes, suggesting that recombinant sequences were present in the data set. Subsequently, five recombinant genomes were identified, four of which contained sequences from either genotype I or II. The population history of vaccine-related genotype II strains was distinct from other aPMV-1 genotypes; genotype II emerged in the late 19th century and is evolving more slowly than other genotypes, which emerged in the 1960s. Despite vaccination efforts, genotype II viruses have experienced constant population growth to the present. In contrast, other contemporary genotypes showed population declines in the late 1990s. Additionally, genotype I and II viruses, which are circulating in the presence of homotypic vaccine pressure, have unique selection profiles compared to nonvaccine-related strains. Collectively, these data show that vaccination with live attenuated viruses has changed the evolution of aPMV-1 by maintaining a large effective population size of a vaccine-related genotype, allowing for coinfection and recombination of vaccine and wild type strains, and by applying unique selective pressures on viral glycoproteins

Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis.

PubMed

Sarkanen, Tomi O; Alakuijala, Anniina P E; Dauvilliers, Yves A; Partinen, Markku M

2018-04-01

An increased incidence of narcolepsy was seen in many countries after the pandemic H1N1 influenza vaccination campaign in 2009-2010. The H1N1 vaccine - narcolepsy connection is based on observational studies that are prone to various biases, e.g., confounding by H1N1 infection, and ascertainment, recall and selection biases. A direct pathogenic link has, however, remained elusive. We conducted a systematic review and meta-analysis to analyze the magnitude of H1N1 vaccination related risk and to examine if there was any association with H1N1 infection itself. We searched all articles from PubMed, Web of Science and Scopus, and other relevant sources reporting the incidence and risk of post-vaccine narcolepsy. In our paper, we show that the risk appears to be limited to only one vaccine (Pandemrix ® ). During the first year after vaccination, the relative risk of narcolepsy was increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults. The vaccine attributable risk in children and adolescents was around 1 per 18,400 vaccine doses. Studies from Finland and Sweden also appear to demonstrate an extended risk of narcolepsy into the second year following vaccination, but such conclusions should be interpreted with a word of caution due to possible biases. Benefits of immunization outweigh the risk of vaccination-associated narcolepsy, which remains a rare disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibody Dynamics of 2009 Influenza A (H1N1) Virus in Infected Patients and Vaccinated People in China

PubMed Central

Liu, Yang; Wu, Jibin; Di, Biao; Chen, Xi; Xu, Xinhong; Lu, Enjie; Li, Kuibiao; Liu, Yanhui; Wu, Yejian; Chen, Xiongfei; He, Peng; Wang, Yulin; Liu, Jianhua

2011-01-01

Background To evaluate the risk of the recurrence and the efficiency of the vaccination, we followed-up antibody responses in patients with the 2009 pandemic H1N1 influenza and persons who received the pandemic H1N1 vaccine in Guangzhou China. Methods We collected serum samples from 129 patients and 86 vaccinated persons at day 0, 15, 30, 180 after the disease onset or the vaccination, respectively. Antibody titers in these serum samples were determined by haemagglutination inhibition (HI) assay using a local isolated virus strain A/Guangdong Liwan/SWL1538/2009(H1N1). Results HI antibody positive rate of the patients increased significantly from 0% to 60% at day 15 (χ2 = 78, P<0.001) and 100% at day 30 (χ2 = 23, P<0.001), but decreased significantly to 52% at day 180 (χ2 = 38, P<0.001), while that of vaccinated subjects increased from 0% to 78% at day 15 (χ2 = 110, P<0.001) and 81% at day 30 (χ2 = 0.32, P = 0.57), but decreased significantly to 34% at day 180 (χ2 = 39, P<0.001). Geometric mean titers (GMT) of HI antibodies in positive samples from the patients did not change significantly between day 15 and day 30 (T = 0.92, P = 0.36), but it decreased significantly from 80 at day 30 to 52 at day 180 (T = 4.5, P<0.001). GMT of vaccinated persons increased significantly from 100 at day 15 to 193 at day 30 (T = 4.5, P<0.001), but deceased significantly to 74 at day 180 (T = 5.1, P<0.001). Compared to the patients, the vaccinated subjects showed lower seroconversion rate (χ2 = 11, P<0.001; χ2 = 5.9, P = 0.015), but higher GMT (T = 6.0, P<0.001; T = 3.6, P = 0.001) at day 30 and day 180, respectively. Conclusion Vaccination of 2009 influenza A (H1N1) was effective. However, about half or more recovered patients and vaccinated persons might have lost sufficient immunity against the recurrence of the viral infection after half a year. Vaccination or re-vaccination may be necessary for

Comparing human papillomavirus vaccine knowledge and intentions among parents of boys and girls

PubMed Central

Lindley, Megan C.; Jeyarajah, Jenny; Yankey, David; Curtis, C. Robinette; Markowitz, Lauri E.; Stokley, Shannon

2016-01-01

ABSTRACT Background/Objective: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Previous research suggests some differences between male and female adolescents in correlates of vaccine receipt and reasons for non-vaccination; few studies examine both sexes together. This analysis assessed knowledge and attitudes related to HPV disease and vaccination, intention to vaccinate, and reasons for delayed vaccination or non-vaccination among parents of boys and girls 13–17 y old in 50 states, the District of Columbia, and selected local areas. Methods: National Immunization Survey-Teen 2013 data were analyzed and gender differences examined. Results: In this sample, adolescent boys were more likely than girls to be unvaccinated and less likely to have completed the HPV vaccination series (p < 0.005 for both). Parents of girls were more likely than parents of boys to report a provider recommendation for HPV vaccination (65.0% vs. 42.1%). Only 29% of girls' parents reported a provider recommendation to begin vaccination by 11–12 y old. Among unvaccinated teens, parental intention to vaccinate in the next 12 months did not differ by sex, but reasons for vaccination or non-vaccination did. Many parents do not know the recommended number of HPV doses. Conclusions: Gender differences in provider vaccination recommendations and reasons for vaccination might partially explain differential HPV uptake by male and female adolescents. Clinicians should offer strong recommendations for HPV vaccination at 11–12 y old for both girls and boys. To reduce missed opportunities, HPV vaccination should be presented in the context of, and given concurrently with, other routinely administered vaccines. PMID:27003108

Exploring human papillomavirus vaccination refusal among ethnic minorities in England: A comparative qualitative study

PubMed Central

Rockliffe, Lauren; Marlow, Laura A.V.; Bedford, Helen; McBride, Emily; Waller, Jo

2017-01-01

Abstract Objectives In England, uptake of human papillomavirus (HPV) vaccination to prevent HPV‐related cancer is lower among girls from ethnic minority backgrounds. We aimed to explore the factors that prevented ethnic minority parents from vaccinating, compared to White British nonvaccinating parents and vaccinating ethnic minority parents. Methods Interviews with 33 parents (n = 14 ethnic minority non‐vaccinating, n = 10 White British nonvaccinating, and n = 9 ethnic minority vaccinating) explored parents' reasons for giving or withholding consent for HPV vaccination. Data were analysed using Framework Analysis. Results Concerns about the vaccine were raised by all nonvaccinating ethnic minority parents, and they wanted information to address these concerns. External and internal influences affected parents' decisions, as well as parents' perceptions that HPV could be prevented using means other than vaccination. Reasons were not always exclusive to nonvaccinating ethnic minority parents, although some were, including a preference for abstinence from sex before marriage. Only ethnic minority parents wanted information provided via workshops. Conclusions Ethnic differences in HPV vaccination uptake may be partly explained by concerns that were only reported by parents from some ethnic groups. Interventions to improve uptake may need to tackle difficult topics like abstinence from sex before marriage, and use a targeted format. PMID:28231418

Characterization of a whole, inactivated influenza (H5N1) vaccine.

PubMed

Tada, Yoshikazu

2008-11-01

Effective vaccines against the highly pathogenic influenza A/H5N1 virus are being developed worldwide. In Japan, two adjuvanted, inactivated, whole-virion influenza vaccines were recently developed and licensed as mock-up, pre-pandemic vaccine formulations by the Ministry of Health and Labor Welfare of Japan. During the vaccine design and development process, various obstacles were overcome and, in this report, we introduce the non clinical production, immunogenicity data in human and development process that was associated with egg-derived adjuvanted, inactivated, whole-virion influenza A (H5N1) vaccine. Pilot lots of H5N1 vaccine were produced using the avirulent H5N1 reference strain A/Vietnam/1194/2004 (H5N1) NIBRG-14 and administered following adsorption with aluminum hydroxide as an adjuvant. Quality control and formulation stability tests were performed before clinical trials were initiated (phase I-III). The research foundation for microbial diseases of Osaka University (BIKEN) carried out vaccine production, quality control, stability testing and the phase I clinical trial in addition to overseeing the licensing of this vaccine. Mitsubishi Chemical Safety Institute Ltd. carried out the non clinical pharmacological toxicity and safety studies and the Japanese medical association carried out the phase II/III trials. Phase I-III trials took place in 2006. The production processes were well controlled by established tests and validations. Vaccine quality was confirmed by quality control, stability and pre-clinical tests, and the vaccine was approved as a mock-up, pre-pandemic vaccine by the Ministry of Health and Labor Welfare of Japan. Numerous safety and efficacy procedures were carried out prior to the approval of the described vaccine formulation. Some of these procedures were of particular importance e.g., vaccine development, validation, and quality control tests that included strict monitoring of the hemagglutinin (HA) content of the vaccine

Safety and immunogenicity of an MF59-adjuvanted A/H1N1 pandemic influenza vaccine in children from three to seventeen years of age.

PubMed

Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans C; Abarca, Katia; Rivera, Luis; Lattanzi, Maria; Pedotti, Paola; Arora, Ashwani; Kieninger-Baum, Dorothee; Della Cioppa, Giovanni

2015-01-01

This study was designed to identify the optimal dose of an MF59-adjuvanted, monovalent, A/H1N1 influenza vaccine in healthy paediatric subjects. Subjects aged 3-8 years (n=194) and 9-17 years (n=160) were randomized to receive two primary doses of A/H1N1 vaccine containing either 3.75 μg antigen with half a standard dose of MF59 adjuvant, 7.5 μg antigen with a full dose of MF59, or (children 3-8 years only), a non-adjuvanted 15 μg formulation. A booster dose of MF59-adjuvanted seasonal influenza vaccine including homologous A/H1N1 strain was given one year after priming. Immunogenicity was assessed by haemagglutination inhibition (HI) and microneutralization assays. Vaccine safety was assessed throughout the study (up to 18 months). A single priming dose of either MF59-adjuvanted formulation was sufficient to meet the European licensure criteria for pandemic influenza vaccines (HI titres ≥1:40>70%; seroconversion>40%; and GMR>2.5). Two non-adjuvanted vaccine doses were required to meet the same licensure criteria. After first and second doses, percentage of subjects with HI titres ≥1:40 were between 97% and 100% in the adjuvanted vaccine groups compared with 68% and 91% in the non-adjuvanted group, respectively. Postvaccination seroconversion rates ranged from 91% to 98% in adjuvanted groups and were 68% (first dose) and 98% (second dose) in the non-adjuvanted group. HI titres ≥1:330 after primary doses were achieved in 69% to 90% in adjuvanted groups compared with 41% in the non-adjuvanted group. Long-term antibody persistence after priming and a robust antibody response to booster immunization were observed in all vaccination groups. All A/H1N1 vaccine formulations were generally well tolerated. No vaccine-related serious adverse events occurred, and no subjects were withdrawn from the study due to an adverse event. An MF59-adjuvanted influenza vaccine containing 3.75 μg of A/H1N1 antigen was well tolerated and sufficiently immunogenic to meet all the

Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals.

PubMed

Kelly, Deborah; Burt, Kimberley; Missaghi, Bayan; Barrett, Lisa; Keynan, Yoav; Fowke, Keith; Grant, Michael

2012-08-31

Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. A single dose of Arepanrix™ split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders. We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals

Complex Immune Correlates of Protection in HIV-1 Vaccine Efficacy Trials

PubMed Central

Tomaras, Georgia D.; Plotkin, Stanley A.

2016-01-01

Summary Development of an efficacious HIV-1 vaccine is a major priority for improving human health worldwide. Vaccine mediated protection against human pathogens can be achieved through elicitation of protective innate, humoral, and cellular responses. Identification of specific immune responses responsible for pathogen protection enables vaccine development and provides insights into host defenses against pathogens and the immunological mechanisms that most effectively fight infection. Defining immunological correlates of transmission risk in preclinical and clinical HIV-1 vaccine trials has moved the HIV-1 vaccine development field forward and directed new candidate vaccine development. Immune correlate studies are providing novel hypotheses about immunological mechanisms that may be responsible for preventing HIV-1 acquisition. Recent results from HIV-1 immune correlates work has demonstrated that there are multiple types of immune responses that together, comprise an immune correlate—thus implicating polyfunctional immune control of HIV-1 transmission. An in depth understanding of these complex immunological mechanisms of protection against HIV-1 will accelerate the development of an efficacious HIV-1 vaccine. PMID:28133811

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective.

PubMed

Abelin, Atika; Colegate, Tony; Gardner, Stephen; Hehme, Norbert; Palache, Abraham

2011-02-01

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness. The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade. During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply. Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure. Enhancing

Onset of immunity in kittens after vaccination with a non-adjuvanted vaccine against feline panleucopenia, feline calicivirus and feline herpesvirus.

PubMed

Jas, D; Aeberlé, C; Lacombe, V; Guiot, A L; Poulet, H

2009-10-01

The induction of a quick onset of immunity against feline parvovirus (FPV), feline herpesvirus (FHV) and feline calicivirus (FCV) is critical both in young kittens after the decline of maternal antibodies and in cats at high risk of exposure. The onset of immunity for the core components was evaluated in 8-9 week old specific pathogen free kittens by challenge 1 week after vaccination with a combined modified live (FPV, FHV) and inactivated (FCV) vaccine. The protection obtained 1 week after vaccination was compared to that obtained when the challenge was performed 3-4 weeks after vaccination. The protocol consisted of a single injection for vaccination against FPV and two injections 4 weeks apart for FHV and FCV. At 1 week after vaccination, the kittens showed no FPV-induced clinical signs or leukopenia following challenge, and after FCV and FHV challenges the clinical score was significantly lower in vaccinated animals than in controls. Interestingly, the relative efficacy of the vaccination was comparable whether the animals were challenged 1 week or 3-4 weeks after vaccination, indicating that the onset of protection occurred within 7 days of vaccination. Following the 1-week challenge, excretion of FPV, FHV and FCV was significantly reduced in vaccinated cats compared to control kittens, confirming the onset of immunity within 7 days of vaccination.

Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk

PubMed Central

Vaarala, Outi; Vuorela, Arja; Partinen, Markku; Baumann, Marc; Freitag, Tobias L.; Meri, Seppo; Saavalainen, Päivi; Jauhiainen, Matti; Soliymani, Rabah; Kirjavainen, Turkka; Olsen, Päivi; Saarenpää-Heikkilä, Outi; Rouvinen, Juha; Roivainen, Merja; Nohynek, Hanna; Jokinen, Jukka; Julkunen, Ilkka; Kilpi, Terhi

2014-01-01

Background Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated. Methods and Findings Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06∶02 risk allele and in DQB1*06∶02 transgenic mice immunized with Pandemrix when compared to controls. Conclusions This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06∶02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins. PMID:25501681

Immunogenicity and tolerability after two doses of non-adjuvanted, whole-virion pandemic influenza A (H1N1) vaccine in HIV-infected individuals.

PubMed

Lagler, Heimo; Grabmeier-Pfistershammer, Katharina; Touzeau-Römer, Veronique; Tobudic, Selma; Ramharter, Michael; Wenisch, Judith; Gualdoni, Guido Andrés; Redlberger-Fritz, Monika; Popow-Kraupp, Theresia; Rieger, Armin; Burgmann, Heinz

2012-01-01

During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1:40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1:40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1:40 or seroconverted after vaccination. The vaccine was well tolerated. The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals.

Immunogenicity and Tolerability after Two Doses of Non-Adjuvanted, Whole-Virion Pandemic Influenza A (H1N1) Vaccine in HIV-Infected Individuals

PubMed Central

Lagler, Heimo; Grabmeier-Pfistershammer, Katharina; Touzeau-Römer, Veronique; Tobudic, Selma; Ramharter, Michael; Wenisch, Judith; Gualdoni, Guido Andrés; Redlberger-Fritz, Monika; Popow-Kraupp, Theresia; Rieger, Armin; Burgmann, Heinz

2012-01-01

Background During the influenza pandemic of 2009/10, the whole-virion, Vero-cell-derived, inactivated, pandemic influenza A (H1N1) vaccine Celvapan® (Baxter) was used in Austria. Celvapan® is adjuvant-free and was the only such vaccine at that time in Europe. The objective of this observational, non-interventional, prospective single-center study was to evaluate the immunogenicity and tolerability of two intramuscular doses of this novel vaccine in HIV-positive individuals. Methods and Findings A standard hemagglutination inhibition (HAI) assay was used for evaluation of the seroconversion rate and seroprotection against the pandemic H1N1 strain. In addition, H1N1-specific IgG antibodies were measured using a recently developed ELISA and compared with the HAI results. Tolerability of vaccination was evaluated up to one month after the second dose. A total of 79 HIV-infected adults with an indication for H1N1 vaccination were evaluated. At baseline, 55 of the 79 participants had an HAI titer ≥1∶40 and two patients showed a positive IgG ELISA. The seroconversion rate was 31% after the first vaccination, increasing to 41% after the second; the corresponding seroprotection rates were 92% and 83% respectively. ELISA IgG levels were positive in 25% after the first vaccination and in 37% after the second. Among the participants with baseline HAI titers <1∶40, 63% seroconverted. Young age was clearly associated with lower HAI titers at baseline and with higher seroconversion rates, whereas none of the seven patients >60 years of age had a baseline HAI titer <1∶40 or seroconverted after vaccination. The vaccine was well tolerated. Conclusion The non-adjuvanted pandemic influenza A (H1N1) vaccine was well tolerated and induced a measurable immune response in a sample of HIV-infected individuals. PMID:22629330

Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations

PubMed Central

Kurtz, Sherry L.

2015-01-01

A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses. PMID:26269537

Calculation of Eddy Currents In the CTH Vacuum Vessel and Coil Frame

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

A. Zolfaghari, A. Brooks, A. Michaels, J. Hanson, and G. Hartwell

2012-09-25

Knowledge of eddy currents in the vacuum vessel walls and nearby conducting support structures can significantly contribute to the accuracy of Magnetohydrodynamics (MHD) equilibrium reconstruction in toroidal plasmas. Moreover, the magnetic fields produced by the eddy currents could generate error fields that may give rise to islands at rational surfaces or cause field lines to become chaotic. In the Compact Toroidal Hybrid (CTH) device (R0 = 0.75 m, a = 0.29 m, B ≤ 0.7 T), the primary driver of the eddy currents during the plasma discharge is the changing flux of the ohmic heating transformer. Electromagnetic simulations are usedmore » to calculate eddy current paths and profile in the vacuum vessel and in the coil frame pieces with known time dependent currents in the ohmic heating coils. MAXWELL and SPARK codes were used for the Electromagnetic modeling and simulation. MAXWELL code was used for detailed 3D finite-element analysis of the eddy currents in the structures. SPARK code was used to calculate the eddy currents in the structures as modeled with shell/surface elements, with each element representing a current loop. In both cases current filaments representing the eddy currents were prepared for input into VMEC code for MHD equilibrium reconstruction of the plasma discharge. __________________________________________________« less

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

PubMed