Evaluation of the Protective Efficacy of Poly I:C as an Adjuvant for H9N2 Subtype Avian Influenza Inactivated Vaccine and Its Mechanism of Action in Ducks

PubMed Central

Zhang, Aiguo; Lai, Hanzhang; Xu, Jiahua; Huang, Wenke; Liu, Yufu; Zhao, Dawei; Chen, Ruiai

2017-01-01

Current commercial H9 avian influenza vaccines cannot provide satisfactory protective immunity against antigenic variant influenza viruses in ducks. Poly I:C, when used as an adjuvant, improves humoral and cellular immunity in many animals but has not been tested in ducks. In this study, we investigated the protective efficacy of Poly I:C as an adjuvant for an inactivated H9N2 Avian influenza vaccine in ducks. We found that an H9N2 vaccine administered with poly I:C (H9-PIC vaccine) induced a significantly more rapid response with higher anti-influenza antibody titers than those of the vaccine alone (H9 vaccine). Moreover, virus shedding was reduced in ducks immunized with the H9-PIC vaccine after challenge with an H9 subtype antigenic variant viruses. IFN-α, IFN-γ, IL-6 and MHC-II mRNA levels were all elevated in ducks receiving the H9-PIC vaccine. In addition, lower expression level of MHC-I may be a reason for inefficient protective ability against heterologous influenza viruses in H9-PIC vaccination of ducks. In conclusion, poly I:C adjuvant enhanced both humoral and cellular immune responses in ducks induced by immunization of inactivated H9N2 vaccine. PMID:28135294

Efficacy of an inactivated bivalent vaccine against the prevalent strains of Newcastle disease and H9N2 avian influenza.

PubMed

Zhao, Jing; Yang, Huiming; Xu, Hongjun; Ma, Zengbin; Zhang, Guozhong

2017-03-16

Newcastle disease (ND) and avian influenza subtype H9N2 (H9N2 AI) are two of the most important diseases of poultry, causing severe economic losses in the global poultry industry. Vaccination is an effective way to prevent and control the spread of ND virus (NDV) and H9N2 AI virus (AIV), but the antigenic differences between the current circulating strains and the vaccine strains might account for recent ND and H9N2 AI outbreaks in vaccinated poultry flocks. We developed an inactivated bivalent H9N2 and NDV vaccine based on the current prevalent strains of H9N2 AIV and NDV in China and evaluated its efficacy in chickens in this study. The results indicated that the inactivated bivalent vaccine could induce a fast antibody response in vaccinated chickens. The hemagglutination inhibition (HI) titer in the sera increased rapidly, and the highest HI titer was observed at 4 weeks post-vaccination (wpv) with a mean titre of 8.6 log 2 for NDV and 9.5 log 2 for H9N2. Up until 15 wpv, HI titers were still detectable at a high level of over 6 log 2 . The immunized chickens showed no signs of disease after challenge at 3 wpv with the prevalent strains of NDV and H9N2 AIV isolated in 2012-2014. Moreover, viral shedding was completely inhibited in vaccinated chickens after challenge with H9N2 AIV and inhibited by at least 90% with NDV compared to the controls at 5dpc. Our findings suggest that the inactivated NDV and H9N2 vaccine induces a fast and strong antibody response in vaccinated chickens and is efficacious in poultry against NDVs and H9N2 AIVs.

Inactivated H9N2 avian influenza virus vaccine with gel-primed and mineral oil-boosted regimen could produce improved immune response in broiler breeders.

PubMed

Lee, D-H; Kwon, J-S; Lee, H-J; Lee, Y-N; Hur, W; Hong, Y-H; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S

2011-05-01

The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.

Heterologous post-infection immunity against Egyptian avian influenza virus (AIV) H9N2 modulates the course of subsequent infection by highly pathogenic AIV H5N1, but vaccination immunity does not.

PubMed

Naguib, Mahmoud M; Grund, Christian; Arafa, Abdel-Satar; Abdelwhab, E M; Beer, Martin; Harder, Timm C

2017-06-01

In Egypt, zoonotic A/goose/Guangdong/1/96 (gs/GD-like) highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.2.1.2 is entrenched in poultry populations and has co-circulated with low-pathogenic avian influenza virus H9N2 of the G1 lineage since 2010. Here, the impact of H9N2 infection or vaccination on the course of consecutive infection with a lethal Egyptian HPAIV H5N1 is studied. Three-week-old chickens were infected with H9N2 or vaccinated with inactivated H9N2 or H5N1 antigens and challenged three weeks later by an HPAIV H5N1. Interestingly, pre-infection of chickens with H9N2 decreased the oral excretion of H5N1 to levels that were comparable to those of H5N1-immunized chickens, but vaccination with inactivated H9N2 did not. H9N2 pre-infection modulated but did not conceal clinical disease by HPAIV H5N1. By contrast, homologous H5 vaccination abolished clinical syndromic surveillance, although vaccinated clinical healthy birds were capable of spreading the virus.

Collaborative studies on the development of national reference standards for potency determination of H7N9 influenza vaccine

PubMed Central

Li, Changgui; Xu, Kangwei; Hashem, Anwar; Shao, Ming; Liu, Shuzhen; Zou, Yong; Gao, Qiang; Zhang, Yongchao; Yuan, Liyong; Xu, Miao; Li, Xuguang; Wang, Junzhi

2015-01-01

The outbreak of human infections of a novel avian influenza virus A (H7N9) prompted the development of the vaccines against this virus. Like all types of influenza vaccines, H7N9 vaccine must be tested for its potency prior to being used in humans. However, the unavailability of international reference reagents for the potency determination of H7N9 vaccines substantially hinders the progress in vaccine development. To facilitate clinical development, we enlisted 5 participants in a collaborative study to develop critical reagents used in Single Radial Immunodiffusion (SRID), the currently acceptable assay for potency determination of influenza vaccine. Specifically, the hemagglutinin (HA) content of one vaccine bulk for influenza A (H7N9), herein designated as Primary Liquid Standard (PLS), was determined by SDS-PAGE. In addition, the freeze-dried antigen references derived from PLS were prepared to enhance the stability for long term storage. The final HA content of lyophilized antigen references were calibrated against PLS by SRID assay in a collaborative study. Importantly, application of these national reference standards to potency analyses greatly facilitated the development of H7N9 vaccines in China. PMID:25970793

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus.

PubMed

Pu, Juan; Wang, Shuoguo; Yin, Yanbo; Zhang, Guozhong; Carter, Robert A; Wang, Jinliang; Xu, Guanlong; Sun, Honglei; Wang, Min; Wen, Chu; Wei, Yandi; Wang, Dongdong; Zhu, Baoli; Lemmon, Gordon; Jiao, Yuannian; Duan, Susu; Wang, Qian; Du, Qian; Sun, Meng; Bao, Jinnan; Sun, Yipeng; Zhao, Jixun; Zhang, Hui; Wu, Gang; Liu, Jinhua; Webster, Robert G

2015-01-13

The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant's internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010-2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.

Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

PubMed

Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

2015-07-01

An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

Current situation of H9N2 subtype avian influenza in China.

PubMed

Gu, Min; Xu, Lijun; Wang, Xiaoquan; Liu, Xiufan

2017-09-15

In China, H9N2 subtype avian influenza outbreak is firstly reported in Guangdong province in 1992. Subsequently, the disease spreads into vast majority regions nationwide and has currently become endemic there. Over vicennial genetic evolution, the viral pathogenicity and transmissibility have showed an increasing trend as year goes by, posing serious threat to poultry industry. In addition, H9N2 has demonstrated significance to public health as it could not only directly infect mankind, but also donate partial or even whole cassette of internal genes to generate novel human-lethal reassortants like H5N1, H7N9, H10N8 and H5N6 viruses. In this review, we mainly focused on the epidemiological dynamics, biological characteristics, molecular phylogeny and vaccine strategy of H9N2 subtype avian influenza virus in China to present an overview of the situation of H9N2 in China.

Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses.

PubMed

Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

2016-02-24

The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses.

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

PubMed Central

Pu, Juan; Wang, Shuoguo; Yin, Yanbo; Zhang, Guozhong; Carter, Robert A.; Wang, Jinliang; Xu, Guanlong; Sun, Honglei; Wang, Min; Wen, Chu; Wei, Yandi; Wang, Dongdong; Zhu, Baoli; Lemmon, Gordon; Jiao, Yuannian; Duan, Susu; Wang, Qian; Du, Qian; Sun, Meng; Bao, Jinnan; Sun, Yipeng; Zhao, Jixun; Zhang, Hui; Wu, Gang; Liu, Jinhua; Webster, Robert G.

2015-01-01

The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential. PMID:25548189

Cross-reactivity between avian influenza A (H7N9) virus and divergent H7 subtypic- and heterosubtypic influenza A viruses

PubMed Central

Guo, Li; Wang, Dayan; Zhou, Hongli; Wu, Chao; Gao, Xin; Xiao, Yan; Ren, Lili; Paranhos-Baccalà, Gláucia; Shu, Yuelong; Jin, Qi; Wang, Jianwei

2016-01-01

The number of human avian H7N9 influenza infections has been increasing in China. Understanding their antigenic and serologic relationships is crucial for developing diagnostic tools and vaccines. Here, we evaluated the cross-reactivities and neutralizing activities among H7 subtype influenza viruses and between H7N9 and heterosubtype influenza A viruses. We found strong cross-reactivities between H7N9 and divergent H7 subtypic viruses, including H7N2, H7N3, and H7N7. Antisera against H7N2, H7N3, and H7N7 could also effectively neutralize two distinct H7N9 strains. Two-way cross-reactivities exist within group 2, including H3 and H4, whereas one-way cross-reactivities were found across other groups, including H1, H10, H9, and H13. Our data indicate that the hemaglutinins from divergent H7 subtypes may facilitate the development of vaccines for distinct H7N9 infections. Moreover, serologic diagnoses for H7N9 infections need to consider possible interference from the cross-reactivity of H7N9 with other subtype influenza viruses. PMID:26907865

Influenza virus-like particles harboring H9N2 HA and NA proteins induce a protective immune response in chicken.

PubMed

Li, Xin; Ju, Houbin; Liu, Jian; Yang, Dequan; Qi, Xinyong; Yang, Xianchao; Qiu, Yafeng; Zheng, Jie; Ge, Feifei; Zhou, Jinping

2017-11-01

Avian influenza viruses represent a growing threat of an influenza pandemic. The co-circulation of multiple H9N2 genotypes over the past decade has been replaced by one predominant genotype-G57 genotype, which displays a changed antigenicity and improved adaptability in chickens. Effective H9N2 subtype avian influenza virus vaccines for poultry are urgently needed. In this study, we constructed H9N2 subtype avian influenza virus-like particle (VLP) and evaluated its protective efficacy in specific pathogen-free (SPF) chickens to lay the foundation for developing an effective vaccine against influenza viruses. Expression of influenza proteins in VLPs was confirmed by Western blot, hemagglutination inhibition (HI), and neuraminidase inhibition (NI). The morphology was observed by electron microscopy. A group of 15 three-week-old SPF chickens was divided into three subgroups of five chickens immunized with VLP, commercial vaccine, and PBS. Challenge study was performed to evaluate efficacy of VLP vaccine. The hemagglutinin (HA) and neuraminidase (NA) proteins were co-expressed in the infected cells, self-assembled, and were released into the culture medium in the form of VLPs of diameter ~80 nm. The VLPs exhibited some functional characteristics of a full influenza virus, including hemagglutination and neuraminidase activity. In SPF chickens, the VLPs elicited serum antibodies specific for H9N2 and induced a higher HI titer (as detected by a homologous antigen) than did a commercial H9N2 vaccine (A/chicken/Shanghai/F/1998). Viral shedding from VLP vaccine subgroup was reduced compared with commercial vaccine subgroup and control subgroup. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice.

PubMed

Wu, Xiao-Xin; Deng, Xi-Long; Yu, Dong-Shan; Yao, Wei; Ou, Hui-Lin; Weng, Tian-Hao; Hu, Chen-Yu; Hu, Feng-Yu; Wu, Nan-Ping; Yao, Hangping; Zhang, Fu-Chun; Li, Lan-Juan

2018-01-01

Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated

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.

Waning vaccine protection against influenza A (H3N2) illness in children and older adults during a single season.

PubMed

Belongia, Edward A; Sundaram, Maria E; McClure, David L; Meece, Jennifer K; Ferdinands, Jill; VanWormer, Jeffrey J

2015-01-01

Recent studies have suggested that vaccine-induced protection against influenza may decline within one season. We reanalyzed data from a study of influenza vaccine effectiveness to determine if time since vaccination was an independent predictor of influenza A (H3N2). Patients with acute respiratory illness were actively recruited during the 2007-2008 season. Respiratory swabs were tested for influenza, and vaccination dates were determined by a validated immunization registry. The association between influenza RT-PCR result and vaccination interval (days) was examined using multivariable logistic regression, adjusting for calendar time, age and other confounders. There were 629 vaccinated participants, including 177 influenza A (H3N2) cases and 452 test negative controls. The mean (SD) interval from vaccination to illness onset was 101.7 (25.9) days for influenza cases and 93.0 (29.9) days for controls. There was a significant association between vaccination interval and influenza result in the main effects model. The adjusted odds ratio (aOR) for influenza was 1.12 (CI 1.01, 1.26) for every 14 day increase in the vaccination interval. Age modified the association between vaccination interval and influenza (p=0.005 for interaction). Influenza was associated with increasing vaccination interval in young children and older adults, but not in adolescents or non-elderly adults. Similar results were found when calendar week of vaccine receipt was assessed as the primary exposure variable. Identification of influenza A (H3N2) was associated with increasing time since vaccination among young children and older adults during a single influenza season. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A novel approach for preparation of the antisera reagent for potency determination of inactivated H7N9 influenza vaccines.

PubMed

Schmeisser, Falko; Jing, Xianghong; Joshi, Manju; Vasudevan, Anupama; Soto, Jackeline; Li, Xing; Choudhary, Anil; Baichoo, Noel; Resnick, Josephine; Ye, Zhiping; McCormick, William; Weir, Jerry P

2016-03-01

The potency of inactivated influenza vaccines is determined using a single-radial immunodiffusion (SRID) assay and requires standardized reagents consisting of a Reference Antigen and an influenza strain-specific antiserum. Timely availability of reagents is a critical step in influenza vaccine production, and the need for backup approaches for reagent preparation is an important component of pandemic preparedness. When novel H7N9 viruses emerged in China in 2013, candidate inactivated H7N9 influenza vaccines were developed for evaluation in clinical trials, and reagents were needed to measure vaccine potency. We previously described an alternative approach for generating strain-specific potency antisera, utilizing modified vaccinia virus Ankara vectors to produce influenza hemagglutinin (HA)-containing virus-like particles (VLPs) for immunization. Vector-produced HA antigen is not dependent upon the success of the traditional bromelain-digestion and HA purification. Antiserum for H7N9 vaccines, produced after immunization of sheep with preparations of bromelain-HA (br-HA), was not optimal for the SRID assay, and the supply of antiserum was limited. However, antiserum obtained from sheep boosted with VLPs containing H7 HA greatly improved the ring quality in the SRID assay. Importantly, this antiserum worked well with both egg- and cell-derived antigen and was distributed to vaccine manufacturers. Utilizing a previously developed approach for preparing vaccine potency antiserum, we have addressed a major bottleneck encountered in preparation of H7N9 vaccine reagents. The combination of br-HA and mammalian VLPs for sequential immunization represents the first use of an alternative approach for producing an influenza vaccine potency antiserum. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.

PubMed

Kim, Shin-Hee

2018-03-09

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.

Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt

PubMed Central

2018-01-01

Highly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry. PMID:29522492

Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

PubMed

Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

2011-09-28

Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

Influenza A(H9N2) Virus, Myanmar, 2014-2015.

PubMed

Lin, Thant Nyi; Nonthabenjawan, Nutthawan; Chaiyawong, Supassama; Bunpapong, Napawan; Boonyapisitsopa, Supanat; Janetanakit, Taveesak; Mon, Pont Pont; Mon, Hla Hla; Oo, Kyaw Naing; Oo, Sandi Myint; Mar Win, Mar; Amonsin, Alongkorn

2017-06-01

Routine surveillance of influenza A virus was conducted in Myanmar during 2014-2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

Improved hatchability and efficient protection after in ovo vaccination with live-attenuated H7N2 and H9N2 avian influenza viruses

PubMed Central

2011-01-01

Mass in ovo vaccination with live attenuated viruses is widely used in the poultry industry to protect against various infectious diseases. The worldwide outbreaks of low pathogenic and highly pathogenic avian influenza highlight the pressing need for the development of similar mass vaccination strategies against avian influenza viruses. We have previously shown that a genetically modified live attenuated avian influenza virus (LAIV) was amenable for in ovo vaccination and provided optimal protection against H5 HPAI viruses. However, in ovo vaccination against other subtypes resulted in poor hatchability and, therefore, seemed impractical. In this study, we modified the H7 and H9 hemagglutinin (HA) proteins by substituting the amino acids at the cleavage site for those found in the H6 HA subtype. We found that with this modification, a single dose in ovo vaccination of 18-day old eggs provided complete protection against homologous challenge with low pathogenic virus in ≥70% of chickens at 2 or 6 weeks post-hatching. Further, inoculation of 19-day old egg embryos with 106 EID50 of LAIVs improved hatchability to ≥90% (equivalent to unvaccinated controls) with similar levels of protection. Our findings indicate that the strategy of modifying the HA cleavage site combined with the LAIV backbone could be used for in ovo vaccination against avian influenza. Importantly, with protection conferred as early as 2 weeks post-hatching, with this strategy birds would be protected prior to or at the time of delivery to a farm or commercial operation. PMID:21255403

A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.

PubMed

Rodriguez, Laura; Nogales, Aitor; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

2017-08-03

Canine influenza viruses (CIVs) cause a contagious respiratory disease in dogs. CIV subtypes include H3N8, which originated from the transfer of H3N8 equine influenza virus (EIV) to dogs; and the H3N2, which is an avian-origin virus adapted to infect dogs. Only inactivated influenza vaccines (IIVs) are currently available against the different CIV subtypes. However, the efficacy of these CIV IIVs is not optimal and improved vaccines are necessary for the efficient prevention of disease caused by CIVs in dogs. Since live-attenuated influenza vaccines (LAIVs) induce better immunogenicity and protection efficacy than IIVs, we have combined our previously described H3N8 and H3N2 CIV LAIVs to create a bivalent vaccine against both CIV subtypes. Our findings show that, in a mouse model of infection, the bivalent CIV LAIV is safe and able to induce, upon a single intranasal immunization, better protection than that induced by a bivalent CIV IIV against subsequent challenge with H3N8 or H3N2 CIVs. These protection results also correlated with the ability of the bivalent CIV LAIV to induce better humoral immune responses. This is the first description of a bivalent LAIV for the control and prevention of H3N8 and H3N2 CIV infections in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Enhanced genetic characterization of influenza A(H3N2) viruses and vaccine effectiveness by genetic group, 2014–2015

PubMed Central

Flannery, Brendan; Zimmerman, Richard K.; Gubareva, Larisa V.; Garten, Rebecca J.; Chung, Jessie R.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Monto, Arnold S.; Ohmit, Suzanne E.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Piedra, Pedro A.; Mishin, Vasiliy P.; Chesnokov, Anton P.; Spencer, Sarah; Thaker, Swathi N.; Barnes, John R.; Foust, Angie; Sessions, Wendy; Xu, Xiyan; Katz, Jacqueline; Fry, Alicia M.

2018-01-01

Background During the 2014–15 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). Methods A novel pyrosequencing assay was used to determine genetic group based on hemagglutinin (HA) gene sequences of influenza A(H3N2) viruses from patients enrolled US Flu Vaccine Effectiveness network sites. Vaccine effectiveness was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. Results Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2); genetic characterization of 1397 viruses showed 1134 (81%) belonged to one HA genetic group (3C.2a) of antigenically drifted H3N2 viruses. Effectiveness of 2014–15 influenza vaccination varied by A(H3N2) genetic group from 1% (95% confidence interval [CI], −14% to 14%) against illness caused by antigenically drifted A(H3N2) group 3C.2a viruses versus 44% (95% CI, 16% to 63%) against illness caused by vaccine-like A(H3N2) group 3C.3b viruses. Conclusion Effectiveness of 2014–15 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in hemagglutinin genes related to antigenic drift were associated with reduced vaccine effectiveness. PMID:27190176

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain.

PubMed

Gherasim, Alin; Martínez-Baz, Iván; Castilla, Jesús; Pozo, Francisco; Larrauri, Amparo

2017-01-01

Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010-2011 season to the 2015-2016 season in Spain. We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

PubMed Central

Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

2016-01-01

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

Effect of previous and current vaccination against influenza A(H1N1)pdm09, A(H3N2), and B during the post-pandemic period 2010-2016 in Spain

PubMed Central

Castilla, Jesús; Pozo, Francisco

2017-01-01

Background Recent studies suggest that the protective effect of the current influenza vaccine could be influenced by vaccination in previous seasons. We estimated the combined effect of the previous and current influenza vaccines from the 2010–2011 season to the 2015–2016 season in Spain. Methods We performed a test-negative case-control study in patients ≥9 years old. We estimated the influenza vaccine effectiveness (IVE) against influenza A(H1N1)pdm09, A(H3N2), and B virus. Results We included 1206 influenza A(H1N1)pdm09 cases, 1358 A(H3N2) cases and 1079 B cases. IVE against A(H1N1)pdm09 virus in the pooled-season analysis was 53% (95% Confidence Interval (CI): 21% to 72%) for those vaccinated only in the current season and 50% (95%CI: 23% to 68%) for those vaccinated in the both current and previous seasons. Against the influenza A(H3N2) virus, IVE was 17% (95%CI: -43% to 52%) for those vaccinated only in the current season and 3% (95%CI: -33% to 28%) for those vaccinated in both seasons. Regarding influenza B, we obtained similar IVEs for those vaccinated only in the current and those vaccinated in both seasons: 57% (95%CI: 12% to 79%) and 56% (95%CI: 36% to 70%), respectively. Conclusion Our results suggested no interference between the previous and current influenza vaccines against A(H1N1)pdm09 and B viruses, but a possible negative interference against A(H3N2) virus. PMID:28614376

Influenza H7N9 and H9N2 Viruses: Coexistence in Poultry Linked to Human H7N9 Infection and Genome Characteristics

PubMed Central

Yu, Xinfen; Jin, Tao; Cui, Yujun; Pu, Xiaoying; Li, Jun; Xu, Jin; Liu, Guang; Jia, Huijue; Liu, Dan; Song, Shili; Yu, Yang; Xie, Li; Huang, Renjie; Ding, Hua; Kou, Yu; Zhou, Yinyan; Wang, Yayu; Xu, Xun; Yin, Ye; Wang, Jian; Guo, Chenyi; Yang, Xianwei; Hu, Liangping; Wu, Xiaopeng; Wang, Hailong; Liu, Jun; Zhao, Guoqiu; Zhou, Jiyong; Gao, George F.; Yang, Ruifu; Wang, Jun

2014-01-01

ABSTRACT Avian influenza virus A of the novel H7N9 reassortant subtype was recently found to cause severe human respiratory infections in China. Live poultry markets were suspected locations of the human H7N9 infection sources, based on the cases' exposure histories and sequence similarities between viral isolates. To explore the role of live poultry markets in the origin of the novel H7N9 virus, we systematically examined poultry and environmental specimens from local markets and farms in Hangzhou, using real-time reverse transcription-PCR (RT-PCR) as well as high-throughput next-generation sequencing (NGS). RT-PCR identified specimens positive for the H7 and N9 genomic segments in all of the 12 poultry markets epidemiologically linked to 10 human H7N9 cases. Chickens, ducks, and environmental specimens from the markets contained heavily mixed subtypes, including H7, N9, H9, and N2 and sometimes H5 and N1. The idea of the coexistence of H7N9 and H9N2 subtypes in chickens was further supported by metagenomic sequencing. In contrast, human H7N9 infection cases (n = 31) were all negative for H9N2 virus according to real-time RT-PCR. The six internal segments were indistinguishable for the H7N9 and H9N2 viruses. The H9, N2, and internal-segment sequences were very close to the sequence of the H9N2 virus circulating in chickens in China recently. Our results provide direct evidence that H9N2 strains coexisted with the novel human-pathogenic H7N9 influenza virus in epidemiologically linked live poultry markets. Avian influenza A virus of the H9N2 subtype likely made a recent contribution to the evolution of the H7N9 virus and continues to do so. IMPORTANCE Our results suggest that avian influenza A virus of the H9N2 subtype likely made a recent contribution to the evolution of the H7N9 virus, a novel reassortant avian influenza virus A subtype, and continues to do so. The finding helps shed light on how the H7N9 virus emerged, spread, and transmitted to humans. It is of

Influenza H7N9 and H9N2 viruses: coexistence in poultry linked to human H7N9 infection and genome characteristics.

PubMed

Yu, Xinfen; Jin, Tao; Cui, Yujun; Pu, Xiaoying; Li, Jun; Xu, Jin; Liu, Guang; Jia, Huijue; Liu, Dan; Song, Shili; Yu, Yang; Xie, Li; Huang, Renjie; Ding, Hua; Kou, Yu; Zhou, Yinyan; Wang, Yayu; Xu, Xun; Yin, Ye; Wang, Jian; Guo, Chenyi; Yang, Xianwei; Hu, Liangping; Wu, Xiaopeng; Wang, Hailong; Liu, Jun; Zhao, Guoqiu; Zhou, Jiyong; Pan, Jingcao; Gao, George F; Yang, Ruifu; Wang, Jun

2014-03-01

Avian influenza virus A of the novel H7N9 reassortant subtype was recently found to cause severe human respiratory infections in China. Live poultry markets were suspected locations of the human H7N9 infection sources, based on the cases' exposure histories and sequence similarities between viral isolates. To explore the role of live poultry markets in the origin of the novel H7N9 virus, we systematically examined poultry and environmental specimens from local markets and farms in Hangzhou, using real-time reverse transcription-PCR (RT-PCR) as well as high-throughput next-generation sequencing (NGS). RT-PCR identified specimens positive for the H7 and N9 genomic segments in all of the 12 poultry markets epidemiologically linked to 10 human H7N9 cases. Chickens, ducks, and environmental specimens from the markets contained heavily mixed subtypes, including H7, N9, H9, and N2 and sometimes H5 and N1. The idea of the coexistence of H7N9 and H9N2 subtypes in chickens was further supported by metagenomic sequencing. In contrast, human H7N9 infection cases (n = 31) were all negative for H9N2 virus according to real-time RT-PCR. The six internal segments were indistinguishable for the H7N9 and H9N2 viruses. The H9, N2, and internal-segment sequences were very close to the sequence of the H9N2 virus circulating in chickens in China recently. Our results provide direct evidence that H9N2 strains coexisted with the novel human-pathogenic H7N9 influenza virus in epidemiologically linked live poultry markets. Avian influenza A virus of the H9N2 subtype likely made a recent contribution to the evolution of the H7N9 virus and continues to do so. Our results suggest that avian influenza A virus of the H9N2 subtype likely made a recent contribution to the evolution of the H7N9 virus, a novel reassortant avian influenza virus A subtype, and continues to do so. The finding helps shed light on how the H7N9 virus emerged, spread, and transmitted to humans. It is of considerable

H2N2 live attenuated influenza vaccine is safe and immunogenic for healthy adult volunteers

PubMed Central

Isakova-Sivak, Irina; Stukova, Marina; Erofeeva, Mariana; Naykhin, Anatoly; Donina, Svetlana; Petukhova, Galina; Kuznetsova, Victoria; Kiseleva, Irina; Smolonogina, Tatiana; Dubrovina, Irina; Pisareva, Maria; Nikiforova, Alexandra; Power, Maureen; Flores, Jorge; Rudenko, Larisa

2015-01-01

H2N2 influenza viruses have not circulated in the human population since 1968, but they are still being regularly detected in the animal reservoir, suggesting their high pandemic potential. To prepare for a possible H2N2 pandemic, a number of H2N2 vaccine candidates have been generated and tested in preclinical and clinical studies. Here we describe the results of a randomized, double-blind placebo-controlled phase 1 clinical trial of an H2N2 live attenuated influenza vaccine (LAIV) candidate prepared from a human influenza virus isolated in 1966. The vaccine candidate was safe and well-tolerated by healthy adults, and did not cause serious adverse events or an increased rate of moderate or severe reactogenicities. The H2N2 vaccine virus was infectious for Humans. It was shed by 78.6% and 74.1% volunteers after the first and second dose, respectively, most probably due to the human origin of the virus. Importantly, no vaccine virus transmission to unvaccinated subjects was detected during the study. We employed multiple immunological tests to ensure the adequate assessment of the H2N2 pandemic LAIV candidate and demonstrated that the majority (92.6%) of the vaccinated subjects responded to the H2N2 LAIV in one or more immunological tests, including 85.2% of subjects with antibody responses and 55.6% volunteers with cell-mediated immune responses. In addition, we observed strong correlation between the H2N2 LAIV virus replication in the upper respiratory tract and the development of antibody responses. PMID:25831405

Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

PubMed Central

Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

2016-01-01

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

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

Recombinant Newcastle Disease Virus Expressing H9 HA Protects Chickens against Heterologous Avian Influenza H9N2 Virus Challenge

PubMed Central

Nagy, Abdou; Lee, Jinhwa; Mena, Ignacio; Henningson, Jamie; Li, Yuhao; Ma, Jingjiao; Duff, Michael; Li, Yonghai; Lang, Yuekun; Yang, Jianmei; Abdallah, Fatma; Richt, Juergen; Ali, Ahmed; García-Sastre, Adolfo; Ma, Wenjun

2017-01-01

In order to produce an efficient poultry H9 avian influenza vaccine that provides cross-protection against multiple H9 lineages, two Newcastle Disease Virus (NDV) LaSota vaccine strain recombinant viruses were generated using reverse genetics. The recombinant NDV-H9Con virus expresses a consensus-H9 hemagglutinin (HA) that is designed based on available H9N2 sequences from Chinese and Middle Eastern isolates. The recombinant NDV-H9Chi virus expresses a chimeric-H9 HA in which the H9 ectodomain of A/Guinea Fowl/Hong Kong/WF10/99 was fused with the cytoplasmic and transmembrane domain of the fusion protein (F) of NDV. Both recombinant viruses expressed the inserted HA stably and grew to high titers. An efficacy study in chickens showed that both recombinant viruses were able to provide protection against challenge with a heterologous H9N2 virus. In contrast to the NDV-H9Chi virus, the NDV-H9Con virus induced a higher hemagglutination inhibition titer against both NDV and H9 viruses in immunized birds, and efficiently inhibited virus shedding through the respiratory route. Moreover, sera collected from birds immunized with either NDV-H9Con or NDV-H9Chi were able to cross-neutralize two different lineages of H9N2 viruses, indicating that NDV-H9Con and NDV-H9Chi are promising vaccine candidates that could provide cross-protection among different H9N2 lineage viruses. PMID:27102817

Avian influenza virus H9N2 infections in farmed minks.

PubMed

Zhang, Chuanmei; Xuan, Yang; Shan, Hu; Yang, Haiyan; Wang, Jianlin; Wang, Ke; Li, Guimei; Qiao, Jian

2015-11-02

The prevalence of avian H9N2 viruses throughout Asia, along with their demonstrated ability to infect mammals, puts them high on the list of influenza viruses with pandemic potential for humans. In this study, we investigated whether H9N2 viruses could infect farmed minks. First, we conducted a serological survey for avian influenza virus antibodies on a random sample of the field-trial population of farmed minks. Then we inoculated farmed minks with A/Chicken/Hebei/4/2008 H9N2 viruses and observed the potential pathogenicity of H9N2 virus and virus shedding in infected minks. H9 influenza antibodies could be detected in most farmed minks with a higher seropositivity, which indicated that farmed minks had the high prevalence of exposure to H9 viruses. After infection, the minks displayed the slight clinical signs including lethargy and initial weight loss. The infected lungs showed the mild diffuse pneumonia with thickened alveolar walls and inflammatory cellular infiltration. Influenza virus detection showed that viruses were detected in the allantoic fluids inoculated supernatant of lung tissues at 3 and 7 days post-infection (dpi), and found in the nasal swabs of H9N2-infected minks at 3-11 dpi, suggesting that H9N2 viruses replicated in the respiratory organ, were then shed outwards. HI antibody test showed that antibody levels began to rise at 7 dpi. Our data provided the serological and experimental evidences that strongly suggested farmed minks under the natural state were susceptible to H9N2 viral infection and might be the H9N2 virus carriers. It is imperative to strengthen the H9N2 viral monitoring in farmed minks and pay urgent attention to prevent and control new influenza viruses pandemic prevalence.

Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.

PubMed

Pillet, S; Racine, T; Nfon, C; Di Lenardo, T Z; Babiuk, S; Ward, B J; Kobinger, G P; Landry, N

2015-11-17

In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against

Intramuscular and intranasal immunization with an H7N9 influenza virus-like particle vaccine protects mice against lethal influenza virus challenge.

PubMed

Ren, Zhiguang; Zhao, Yongkun; Liu, Jing; Ji, Xianliang; Meng, Lingnan; Wang, Tiecheng; Sun, Weiyang; Zhang, Kun; Sang, Xiaoyu; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Hualei; Yang, Songtao; Yang, Zhengyan; Ma, Yuanfang; Gao, Yuwei; Xia, Xianzhu

2018-05-01

The H7N9 influenza virus epidemic has been associated with a high mortality rate in China. Therefore, to prevent the H7N9 virus from causing further damage, developing a safe and effective vaccine is necessary. In this study, a vaccine candidate consisting of virus-like particles (VLPs) based on H7N9 A/Shanghai/2/2013 and containing hemagglutinin (HA), neuraminidase (NA), and matrix protein (M1) was successfully produced using a baculovirus (BV) expression system. Immunization experiments showed that strong humoral and cellular immune responses could be induced by the developed VLPs when administered via either the intramuscular (IM) or intranasal (IN) immunization routes. Notably, VLPs administered via both immunization routes provided 100% protection against lethal infection caused by the H7N9 virus. The IN immunization with 40μg of H7N9 VLPs induced strong lung IgA and lung tissue resident memory (TRM) cell-mediated local immune responses. These results provide evidence for the development of an effective preventive vaccine against the H7N9 virus based on VLPs administered through both the IM and IN immunization routes. Copyright © 2017. Published by Elsevier B.V.

A single immunization with modified vaccinia virus Ankara-based influenza virus H7 vaccine affords protection in the influenza A(H7N9) pneumonia ferret model.

PubMed

Kreijtz, Joost H C M; Wiersma, Lidewij C M; De Gruyter, Heidi L M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; Stittelaar, Koert J; Fouchier, Ron A M; Osterhaus, Albert D M E; Sutter, Gerd; Rimmelzwaan, Guus F

2015-03-01

Since the first reports in early 2013, >440 human cases of infection with avian influenza A(H7N9) have been reported including 122 fatalities. After the isolation of the first A(H7N9) viruses, the nucleotide sequences became publically available. Based on the coding sequence of the influenza virus A/Shanghai/2/2013 hemagglutinin gene, a codon-optimized gene was synthesized and cloned into a recombinant modified vaccinia virus Ankara (MVA). This MVA-H7-Sh2 viral vector was used to immunize ferrets and proved to be immunogenic, even after a single immunization. Subsequently, ferrets were challenged with influenza virus A/Anhui/1/2013 via the intratracheal route. Unprotected animals that were mock vaccinated or received empty vector developed interstitial pneumonia characterized by a marked alveolitis, accompanied by loss of appetite, weight loss, and heavy breathing. In contrast, animals vaccinated with MVA-H7-Sh2 were protected from severe disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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.

Complete genome sequence of a novel H9N2 subtype influenza virus FJG9 strain in China reveals a natural reassortant event.

PubMed

Xie, Qingmei; Yan, Zhuanqiang; Ji, Jun; Zhang, Huanmin; Liu, Jun; Sun, Yue; Li, Guangwei; Chen, Feng; Xue, Chunyi; Ma, Jingyun; Bee, Yingzuo

2012-09-01

A/chicken/FJ/G9/09 (FJ/G9) is an H9N2 subtype avian influenza virus (H9N2 AIV) strain causing high morbidity that was isolated from broilers in Fujian Province of China in 2009. FJ/G9 has been used as the vaccine strain against H9N2 AIV infection in Fujian Province of China. Here, we report the complete genome sequence of FJ/G9 with natural six-way reassortment, which is the most complex genotype strain in China and even in the world so far. The present findings will aid in understanding the complexity and diversity of H9N2 subtype avian influenza virus.

Health and economic benefits of early vaccination and nonpharmaceutical interventions for a human influenza A (H7N9) pandemic: a modeling study.

PubMed

Khazeni, Nayer; Hutton, David W; Collins, Cassandra I F; Garber, Alan M; Owens, Douglas K

2014-05-20

Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness. To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1). Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city. Literature and expert opinion. Residents of a U.S. metropolitan city with characteristics similar to New York City. Lifetime. Societal. Vaccination of 30% of the population at 4 or 6 months. Infections and deaths averted and cost-effectiveness. In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million. If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months. The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions. Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing non-pharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available. Agency for Healthcare Research and Quality, National Institutes of Health, and Department of Veterans Affairs.

Complete genome sequence of a novel H9N2 subtype influenza virus FJG9 strain in china reveals a natural reassortant event

USDA-ARS?s Scientific Manuscript database

A Chicken/FJ/G9/09 (FJ/G9) is an H9N2 subtype strain of avian influenza virus (H9N2 AIV) strain causing high morbidity, that was isolated from broilers in Fujian province, China, in 2009. The FJ/G9 has been used as the vaccine strain against H9N2 AIV infection in Fujian Province of China. Here, we r...

Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine.

PubMed

Qiu, Chao; Huang, Yang; Wang, Qian; Tian, Di; Zhang, Wanju; Hu, Yunwen; Yuan, Zhenghong; Zhang, Xiaoyan; Xu, Jianqing

2012-01-01

A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations.

Antigenic evolution of H9N2 chicken influenza viruses isolated in China during 2009-2013 and selection of a candidate vaccine strain with broad cross-reactivity.

PubMed

Wei, Yandi; Xu, Guanlong; Zhang, Guozhong; Wen, Chu; Anwar, Furkat; Wang, Shuoguo; Lemmon, Gordon; Wang, Jinliang; Carter, Robert; Wang, Min; Sun, Honglei; Sun, Yipeng; Zhao, Jixun; Wu, Gang; Webster, Robert G; Liu, Jinhua; Pu, Juan

2016-01-01

We previously demonstrated that H9N2 subtype avian influenza viruses (AIVs) isolated from 1994 to 2008 evolved into distinct antigenic groups (C, D, and E) and then underwent antigenic drift from commercial vaccines, causing a country-wide outbreak during 2010-2013. In this study, H9N2 AIVs isolated from chickens during 2009-2013 were antigenically analyzed by performing hemagglutination inhibition and neutralization assays using a panel of polyclonal antibodies. Our findings confirmed the antigenic drift of recent H9N2 viruses from the commercial vaccine and showed that most of these antigenic variants form a novel HI antigenic group, F, with a few belonging to groups D and E. Slight antigenic variation was observed in group F viruses. Genetic analysis of amino acid sequences deduced from hemagglutinin (HA) gene sequences indicated that 9 of 15 mutations predominant in the 2009-2013 viruses can be mapped to known antigenic sites, which might be responsible for the novel antigenicity of group F. These antigenic changes make it necessary to modify the influenza vaccine to ensure efficient protection. A vaccine candidate, Ck/HeB/YT/10, was selected and provided significant protection against viruses from different antigenic groups in terms of reduction in virus shedding, suggesting broad cross-reactivity. Taken together, our results indicate that the H9N2 chicken influenza viruses in China have evolved from distinct antigenic groups into a novel group F that became dominant during the country-wide outbreak and now seems to be undergoing new antigenic divergence. Systematic surveillance and timely updating of vaccine strains are important for viral prevention and control in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

Antigenic evolution of H9N2 chicken influenza viruses isolated in China during 2009–2013 and selection of a candidate vaccine strain with broad cross-reactivity

PubMed Central

Wei, Yandi; Xu, Guanlong; Zhang, Guozhong; Wen, Chu; Anwar, Furkat; Wang, Shuoguo; Lemmon, Gordon; Wang, Jinliang; Carter, Robert; Wang, Min; Sun, Honglei; Sun, Yipeng; Zhao, Jixun; Wu, Gang; Webster, Robert G.; Liu, Jinhua; Pu, Juan

2016-01-01

We previously demonstrated that H9N2 subtype avian influenza viruses (AIVs) isolated from 1994 to 2008 evolved into distinct antigenic groups (C, D, and E) and then underwent antigenic drift from commercial vaccines, causing a country-wide outbreak during 2010–2013. In this study, H9N2 AIVs isolated from chickens during 2009–2013 were antigenically analyzed by performing hemagglutination inhibition and neutralization assays using a panel of polyclonal antibodies. Our findings confirmed the antigenic drift of recent H9N2 viruses from the commercial vaccine and showed that most of these antigenic variants form a novel HI antigenic group, F, with a few belonging to groups D and E. Slight antigenic variation was observed in group F viruses. Genetic analysis of amino acid sequences deduced from hemagglutinin (HA) gene sequences indicated that 9 of 15 mutations predominant in the 2009–2013 viruses can be mapped to known antigenic sites, which might be responsible for the novel antigenicity of group F. These antigenic changes make it necessary to modify the influenza vaccine to ensure efficient protection. A vaccine candidate, Ck/HeB/YT/10, was selected and provided significant protection against viruses from different antigenic groups in terms of reduction in virus shedding, suggesting broad cross-reactivity. Taken together, our results indicate that the H9N2 chicken influenza viruses in China have evolved from distinct antigenic groups into a novel group F that became dominant during the country-wide outbreak and now seems to be undergoing new antigenic divergence. Systematic surveillance and timely updating of vaccine strains are important for viral prevention and control in the future. PMID:26711021

Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

PubMed Central

Naggar, Heba M. El; Madkour, Mohamed Sayed; Hussein, Hussein Ali

2017-01-01

Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND) and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2) based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles Montanide™ adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2) viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses. PMID:28344402

Poultry vaccination directed evolution of H9N2 low pathogenicity avian influenza viruses in Korea

USDA-ARS?s Scientific Manuscript database

Significant economic losses in the poultry industries have resulted from H9N2 low pathogenic avian influenza virus infections across North Africa, the Middle East and Asia. The present study investigated the evolutionary dynamics of H9N2 viruses circulating in Korea from 1996 to 2012. Our analysis o...

Memory T-cell immune response in healthy young adults vaccinated with live attenuated influenza A (H5N2) vaccine.

PubMed

Chirkova, T V; Naykhin, A N; Petukhova, G D; Korenkov, D A; Donina, S A; Mironov, A N; Rudenko, L G

2011-10-01

Cellular immune responses of both CD4 and CD8 memory/effector T cells were evaluated in healthy young adults who received two doses of live attenuated influenza A (H5N2) vaccine. The vaccine was developed by reassortment of nonpathogenic avian A/Duck/Potsdam/1402-6/68 (H5N2) and cold-adapted A/Leningrad/134/17/57 (H2N2) viruses. T-cell responses were measured by standard methods of intracellular cytokine staining of gamma interferon (IFN-γ)-producing cells and a novel T-cell recognition of antigen-presenting cells by protein capture (TRAP) assay based on the trogocytosis phenomenon, namely, plasma membrane exchange between interacting immune cells. TRAP enables the detection of activated trogocytosis-positive T cells after virus stimulation. We showed that two doses of live attenuated influenza A (H5N2) vaccine promoted both CD4 and CD8 T-memory-cell responses in peripheral blood of healthy young subjects in the clinical study. Significant differences in geometric mean titers (GMTs) of influenza A (H5N2)-specific IFN-γ(+) cells were observed at day 42 following the second vaccination, while peak levels of trogocytosis(+) T cells were detected earlier, on the 21st day after the second vaccination. The inverse correlation of baseline levels compared to postvaccine fold changes in GMTs of influenza-specific CD4 and CD8 T cells demonstrated that baseline levels of these specific cells could be considered a predictive factor of vaccine immunogenicity.

PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

PubMed Central

Xiao, Chencheng; Ma, Wenjun; Sun, Na; Huang, Lihong; Li, Yaling; Zeng, Zhaoyong; Wen, Yijun; Zhang, Zaoyue; Li, Huanan; Li, Qian; Yu, Yuandi; Zheng, Yi; Liu, Shukai; Hu, Pingsheng; Zhang, Xu; Ning, Zhangyong; Qi, Wenbao; Liao, Ming

2016-01-01

Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts. PMID:26782141

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

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

Pushko, Peter, E-mail: ppushko@medigen-usa.com

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes.more » All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. - Highlights: •VLPs were prepared that co-localized H5, H7 and H9 subtypes in a VLP envelope. •VLPs were characterized including electron microscopy, HA assay and NA enzyme activity. •Experimental VLP vaccine was evaluated in an avian influenza challenge model. •VLPs induced immune responses against heterologous H5, H7 and H9 virus challenges.« less

Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study

PubMed Central

McVernon, Jodie; Laurie, Karen; Barr, Ian; Kelso, Anne; Skeljo, Maryanne; Nolan, Terry

2010-01-01

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background  Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives  In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods  Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results  Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions  Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings

Potency of an inactivated influenza vaccine prepared from A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice

PubMed Central

SUZUKI, Mizuho; OKAMATSU, Masatoshi; HIONO, Takahiro; MATSUNO, Keita; SAKODA, Yoshihiro

2017-01-01

H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries. Sufficient neutralizing antibodies against homologous and heterologous viruses were induced in mice after two subcutaneous injections of the inactivated whole virus particle vaccine. The inactivated vaccine induced protective immunity sufficient to reduce the impact of challenges with A/swine/Missouri/2124514/2006 (H2N3). This study demonstrates that the inactivated whole virus particle vaccine prepared from an influenza virus library would be useful against a future H2 influenza pandemic. PMID:28993601

Interim estimates of the effectiveness of the influenza vaccine against A(H3N2) influenza in adults in South Korea, 2016-2017 season.

PubMed

Noh, Ji Yun; Lim, Sooyeon; Song, Joon Young; Choi, Won Suk; Jeong, Hye Won; Heo, Jung Yeon; Lee, Jacob; Seo, Yu Bin; Lee, Jin-Soo; Wie, Seong Heon; Kim, Young Keun; Park, Kyung Hwa; Jung, Sook-In; Kim, Shin Woo; Lee, Sun Hee; Lee, Han Sol; Yoon, Young Hoon; Cheong, Hee Jin; Kim, Woo Joo

2017-01-01

In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

Transmissibility of novel H7N9 and H9N2 avian influenza viruses between chickens and ferrets.

PubMed

Ku, Keun Bon; Park, Eun Hye; Yum, Jung; Kim, Heui Man; Kang, Young Myong; Kim, Jeong Cheol; Kim, Ji An; Kim, Hyun Soo; Seo, Sang Heui

2014-02-01

Previous studies have shown that the H7N9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. Here, we studied the infectivity of the H7N9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. The H7N9 virus (A/Anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. H7N9 virus was shed from chicken tracheae for only 2 days after infection and from chicken cloacae for only 1 day after infection, while the H9N2 avian influenza virus, which is endemic in chickens in many Asian countries, was shed from tracheae and cloacae for 8 days after infection. Taken together, our results suggest that chickens may be a poor agent of transmission for the H7N9 virus to other chickens and to mammals, including humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

PubMed Central

Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M.; Kapczynski, Darrell R.

2016-01-01

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. PMID:27936463

Molecular epidemiology of H9N2 influenza viruses in Northern Europe.

PubMed

Lindh, Erika; Ek-Kommonen, Christine; Väänänen, Veli-Matti; Vaheri, Antti; Vapalahti, Olli; Huovilainen, Anita

2014-08-27

Low pathogenic avian influenza viruses are maintained in wild bird populations throughout the world. Avian influenza viruses are characterized by their efficient ability to reassort and adapt, which enables them to cross the species barrier and enhances their zoonotic potential. Influenza viruses of the H9N2 subtype appear endemic among poultry in Eurasia. They usually exist as low-pathogenic strains and circulate between wild bird populations, poultry and birds sold at live bird markets. Direct transmission of H9N2 viruses, with receptor specificities similar to human influenza strains, to pigs and humans has been reported on several occasions. H9N2 virus was first encountered in Finland in 2009, during routine screening of hunted wild waterfowl. The next year, H9N2 influenza viruses were isolated from wild birds on four occasions, including once from a farmed mallard. We have investigated the relationship between the reared and wild bird isolates by sequencing the hemagglutinin and the neuraminidase genes of the Finnish H9N2 viruses. Nucleotide sequence comparison and phylogenetic analyses indicate that H9N2 was transmitted from wild birds to reared birds in 2010, and that highly identical strains have been circulating in Europe during the last few years. Copyright © 2014 Elsevier B.V. All rights reserved.

Construction of a recombinant duck enteritis virus vaccine expressing hemagglutinin of H9N2 avian influenza virus and evaluation of its efficacy in ducks.

PubMed

Sun, Ying; Yang, Chenghuai; Li, Junping; Li, Ling; Cao, Minghui; Li, Qihong; Li, Huijiao

2017-01-01

H9 subtype avian influenza viruses (AIVs) remain a significant burden in the poultry industry and are considered to be one of the most likely causes of any new influenza pandemic in humans. As ducks play an important role in the maintenance of H9 viruses in nature, successful control of the spread of H9 AIVs in ducks will have significant beneficial effects on public health. Duck enteritis virus (DEV) may be a promising candidate viral vector for aquatic poultry vaccination. In this study, we constructed a recombinant DEV, rDEV-∆UL2-HA, inserting the hemagglutinin (HA) gene from duck-origin H9N2 AIV into the UL2 gene by homologous recombination. One-step growth analyses showed that the HA gene insertion had no effect on viral replication and suggested that the UL2 gene was nonessential for virus growth in vitro. In vivo tests further showed that the insertion of the HA gene in place of the UL2 gene did not affect the immunogenicity of the virus. Moreover, a single dose of 10 3 TCID 50 of rDEV-∆UL2-HA induced solid protection against lethal DEV challenge and completely prevented H9N2 AIV viral shedding. To our knowledge, this is the first report of a DEV-vectored vaccine providing robust protection against both DEV and H9N2 AIV virus infections in ducks.

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.

Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses

PubMed Central

Kapczynski, Darrell R.; Tumpey, Terrence M.; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tretyakova, Irina; Pushko, Peter

2016-01-01

Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co-expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus. PMID:26868083

Vaccine Efficacy Against a New Avian Influenza (H9N2) Field Isolate from the Middle East (Serology and Challenge Studies).

PubMed

Gharaibeh, Saad; Amareen, Shadi

2016-05-01

Avian influenza subtype H9N2 is endemic in many countries in the Middle East. The reported prevalence of infection was variable between countries and ranged from 28.7% in Tunisia to 71% in Jordan. Several commercial killed whole-virus vaccine products are used as monovalent or bivalent mixed with Newcastle disease virus. Recently, we have noticed that many of the vaccinated broiler flocks did not show a production advantage over nonvaccinated flocks in the field. A new avian influenza field virus (H9N2) was isolated from these vaccinated and infected broiler flocks in 2013. This virus had 89.1% similarity of its hemagglutinin (HA) gene to the classical virus used for manufacturing the classical vaccine. Inactivated autogenous vaccine was manufactured from this new field isolate to investigate its serological response and protection in specific-pathogen-free (SPF) and breeder-male chickens compared to the classical vaccine. Oropharyngeal virus shedding of vaccinated breeder-male chickens was evaluated at 3, 9, 10, and 14 days postchallenge (DPC). Percentage of chickens shedding the virus at 3 DPC was 64%, 50%, and 64% in the classical vaccine group, autogenous vaccine group, and the control challenged group, respectively. At 7 DPC percentage of virus shedding was 42%, 7%, and 64% in the classical vaccine group, autogenous vaccine group, and the control challenged group, respectively. At 10 DPC only 9% of classical vaccine group was shedding the virus and there was no virus shedding in any of the groups at 14 DPC. There was statistical significance difference (P < 0.05) in shedding only at 7 DPC between the autogenous vaccine group and the other two groups. At 42 days of age (14 DPC), average body weight was 2.720, 2.745, 2.290, and 2.760 kg for the classical vaccine group, autogenous vaccine group, control challenged group, and control unchallenged group, respectively. Only the control challenged group had significantly (P < 0.05) lower average body weight. In

Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

PubMed

Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

2016-07-19

Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influenza Viral Vectors Expressing Two Kinds of HA Proteins as Bivalent Vaccine Against Highly Pathogenic Avian Influenza Viruses of Clade 2.3.4.4 H5 and H7N9

PubMed Central

Li, Jinping; Hou, Guangyu; Wang, Yan; Wang, Suchun; Peng, Cheng; Yu, Xiaohui; Jiang, Wenming

2018-01-01

The H5 and H7N9 subtypes of highly pathogenic avian influenza viruses (HPAIVs) in China pose a serious challenge to public health and the poultry industry. In this study, a replication competent recombinant influenza A virus of the Í5N1 subtype expressing the H7 HA1 protein from a tri-cistronic NS segment was constructed. A heterologous dimerization domain was used to combine with the truncated NS1 protein of 73 amino acids to increase protein stability. H7 HA1, nuclear export protein coding region, and the truncated NS1 were fused in-frame into a single open reading frame via 2A self-cleaving peptides. The resulting PR8-H5-NS1(73)H7 stably expressed the H5 HA and H7 HA1 proteins, and exhibited similar growth kinetics as the parental PR8-H5 virus in vitro. PR8-H5-NS1(73)H7 induced specific hemagglutination inhibition (HI) antibody against H5, which was comparable to that of the combination vaccine of PR8-H5 and PR8-H7. The HI antibody titers against H7 virus were significantly lower than that by the combination vaccine. PR8-H5-NS1(73)H7 completely protected chickens from challenge with both H5 and H7 HPAIVs. These results suggest that PR8-H5-NS1(73)H7 is highly immunogenic and efficacious against both H5 and H7N9 HPAIVs in chickens. Highlights: - PR8-H5-NS1(73)H7 simultaneously expressed two HA proteins of different avian influenza virus subtypes. - PR8-H5-NS1(73)H7 was highly immunogenic in chickens. - PR8-H5-NS1(73)H7 provided complete protection against challenge with both H5 and H7N9 HPAIVs. PMID:29670587

Isolation and characterization of an H9N2 influenza virus isolated in Argentina

PubMed Central

Xu, Kemin; Ferreri, Lucas; Rimondi, Agustina; Olivera, Valeria; Romano, Marcelo; Ferreyra, Hebe; Rago, Virgina; Uhart, Marcela; Chen, Hongjun; Sutton, Troy; Pereda, Ariel; Perez, Daniel R.

2016-01-01

As part of our ongoing efforts on animal influenza surveillance in Argentina, an H9N2 virus was isolated from a wild aquatic bird (Netta peposaca), A/rosy-billed pochard/Argentina/CIP051-559/2007 (H9N2) – herein referred to as 559/H9N2. Due to the important role that H9N2 viruses play in the ecology of influenza in nature, the 559/H9N2 isolate was characterized molecularly and biologically. Phylogenetic analysis of the HA gene revealed that the 559/H9N2 virus maintained an independent evolutionary pathway and shared a sister-group relationship with North American viruses, suggesting a common ancestor. The rest of the genome segments clustered with viruses from South America. Experimental inoculation of the 559/H9N2 in chickens and quail revealed efficient replication and transmission only in quail. Our results add to the notion of the unique evolutionary trend of avian influenza viruses in South America. Our study increases our understanding of H9N2 viruses in nature and emphasizes the importance of expanding animal influenza surveillance efforts to better define the ecology of influenza viruses at a global scale. PMID:22709552

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens.

PubMed

Pushko, Peter; Tretyakova, Irina; Hidajat, Rachmat; Zsak, Aniko; Chrzastek, Klaudia; Tumpey, Terrence M; Kapczynski, Darrell R

2017-01-15

Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine. Copyright © 2016. Published by Elsevier Inc.

Outbreak of Influenza A(H1N1) in a Kidney Transplant Unit-Protective Effect of Vaccination.

PubMed

Helanterä, I; Anttila, V-J; Lappalainen, M; Lempinen, M; Isoniemi, H

2015-09-01

Seasonal influenza vaccination is recommended for patients with end-stage renal disease (ESRD), despite suggested inferior efficacy among these patients. We characterize an outbreak of influenza A(H1N1) in a kidney transplant unit. Altogether 23 patients were treated on the ward for postoperative care after kidney transplantation during the outbreak. After the first positive case, all patients were tested with nasopharyngeal swab tests and 7 patients were diagnosed with influenza A(H1N1). Altogether 17/23 patients had received adequate seasonal influenza vaccination, of whom 2/17 tested positive for influenza (one asymptomatic, one with mild cough). Five of six unvaccinated patients were diagnosed with influenza A(H1N1); 3/5 suffered from severe respiratory failure and were treated with ventilator support in the ICU, but all died due to acute respiratory distress syndrome, whereas 2/5 suffered from mild viral pneumonitis and recovered fully. The risk of influenza infection and mortality was significantly increased in unvaccinated patients (odds ratio 37.5 [95% CI 2.7-507.5, p = 0.01] and 6.7 [95% CI 2.3-18.9, p = 0.003], respectively). Influenza A(H1N1) had a high mortality in our cohort of nonvaccinated immunosuppressed patients early after kidney transplantation. None of the vaccinated patients developed serious disease, supporting the role of vaccination also for ESRD patients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines.

PubMed

Tu, Liqing; Zhou, Pei; Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

2017-11-17

Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.

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

Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus

PubMed Central

2013-01-01

Background Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. Method In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. Results In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. Conclusion After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can

A Dose-Response Study of Inactivated Low Pathogenic Avian Influenza H9N2 Virus in Specific-Pathogen-Free and Commercial Broiler Chickens.

PubMed

Kilany, Walid H; Ali, Ahmed; Bazid, Abdel-Hamid I; El-Deeb, Ayman H; El-Abideen, Mohamed A Zain; Sayed, Magdy El; El-Kady, Magdy F

2016-05-01

Since the first report of low pathogenic avian influenza (LPAI) H9N2 virus in Egypt in 2011, the Egyptian poultry industry has suffered from unexpected economic losses as a result of the wide spread of LPAI H9N2. Hence, inactivated H9N2 vaccines have been included in the vaccination programs of different poultry production sectors. The optimal antigen content of avian influenza virus vaccines is essential to reach protective antibody titers. In this study, the correlation between antigen content (based on hemagglutinating units [HAU]) and postvaccination (PV) antibody response of H9N2 inactivated vaccine was studied. Five different vaccine antigen loads (128, 200, 250, 300, and 350 HAU formulas/dose) were investigated in commercial broiler and specific-pathogen-free (SPF) chickens. Vaccine safety and PV antibody responses were monitored. At the fourth week PV only SPF vaccinated groups (128, 200, 250, and 300 HAU/dose) were challenged using LPAI H9N2 (A/Ck/EG/114940v/NLQP/11) virus with 10(6) EID50/bird. Oropharyngeal swabs were used to monitor virus shedding at 2, 4, 6, and 10 days postchallenge. Results showed that all vaccine formulations were well tolerated, and the highest antibody titers were observed in birds vaccinated with higher HAU. Vaccines containing 128 and 200 HAU/dose did not induce the required protective HI titers by 3 wk PV. Meanwhile, the challenge experiment in SPF chickens showed that 250 and 300 HAU vaccine doses were required to reduce the level and duration of virus shedding. Study results thus suggest that inactivated H9N2 vaccines containing at least 250 HAU/dose will induce the optimal protective titers and minimize virus shedding in SPF chickens.

Intraspecies and interspecies transmission of mink H9N2 influenza virus.

PubMed

Yong-Feng, Zhao; Fei-Fei, Diao; Jia-Yu, Yu; Feng-Xia, Zhang; Chang-Qing, Jiang; Jian-Li, Wang; Shou-Yu, Guo; Kai, Cui; Chuan-Yi, Liu; Xue-Hua, Wei; Jiang, Shi-Jin; Zhi-Jing, Xie

2017-08-07

H9N2 influenza A virus (IAV) causes low pathogenic respiratory disease and infects a wide range of hosts. In this study, six IAVs were isolated from mink and identified as H9N2 IAV. Sequence analysis revealed that the six isolates continued to evolve, and their PB2 genes shared high nucleotide sequence identity with H7N9 IAV. The six isolates contained an amino acid motif PSRSSR↓GL at the hemagglutinin cleavage site, which is a characteristic of low pathogenic influenza viruses. A serosurvey demonstrated that H9N2 IAV had spread widely in mink and was prevalent in foxes and raccoon dogs. Transmission experiments showed that close contact between H9N2-infected mink and naive mink, foxes and raccoon dogs resulted in spread of the virus to the contact animals. Furthermore, H9N2 challenge experiments in foxes and raccoon dogs showed that H9N2 IAV could infect these hosts. Virological and epidemiological surveillance of H9N2 IAV should be strengthened for the fur animal industry.

Stockpiled pre-pandemic H5N1 influenza virus vaccines with AS03 adjuvant provide cross-protection from H5N2 clade 2.3.4.4 virus challenge in ferrets

PubMed Central

Sun, Xiangjie; Belser, Jessica A.; Pulit-Penaloza, Joanna A.; Creager, Hannah M.; Guo, Zhu; Jefferson, Stacie N.; Liu, Feng; York, Ian A.; Stevens, James; Maines, Taronna R.; Jernigan, Daniel B.; Katz, Jacqueline M.; Levine, Min Z.; Tumpey, Terrence M.

2018-01-01

Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed. Here, we selected two AS03-adjuvanted H5N1 vaccines from the US national prepandemic influenza vaccine stockpile and assessed whether the 2004–05 vaccines could provide protection against a 2014 highly pathogenic avian influenza (HPAI) H5N2 virus (A/northern pintail/Washington/40964/2014), a clade 2.3.4.4 virus responsible for mass culling of poultry in North America. Ferrets received two doses of adjuvanted vaccine containing 7.5 μg of hemagglutinin (HA) from A/Vietnam/1203/2004 (clade 1) or A/Anhui/1/2005 (clade 2.3.4) virus either in a homologous or heterologous prime-boost vaccination regime. We found that both vaccination regimens elicited robust antibody responses against the 2004–05 vaccine viruses and could reduce virus-induced morbidity and viral replication in the lower respiratory tract upon heterologous challenge despite the low level of cross-reactive antibody titers to the challenge H5N2 virus. This study supports the value of existing stockpiled 2004–05 influenza H5N1 vaccines, combined with AS03-adjuvant for early use in the event of an emerging pandemic with H5N2-like clade 2.3.4.4 viruses. PMID:28554058

Swine influenza virus vaccine serologic cross-reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v.

PubMed

Kitikoon, Pravina; Gauger, Phillip C; Anderson, Tavis K; Culhane, Marie R; Swenson, Sabrina; Loving, Crystal L; Perez, Daniel R; Vincent, Amy L

2013-12-01

Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross-reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines

PubMed Central

Li, Lutao; Li, Xiuzhen; Hu, Renjun; Jia, Kun; Sun, Lingshuang; Yuan, Ziguo; Li, Shoujun

2017-01-01

Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease. PMID:29228675

Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

PubMed Central

Kissling, Esther; Rondy, Marc

2017-01-01

We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0–14, 15–64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65–79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2). PMID:28230524

Avian influenza A (H7N9) virus infection in humans: epidemiology, evolution, and pathogenesis.

PubMed

Husain, Matloob

2014-12-01

New human influenza A virus strains regularly emerge causing seasonal epidemics and occasional pandemics. Lately, several zoonotic avian influenza A strains have been reported to directly infect humans. In early 2013, a novel avian influenza A virus (H7N9) strain was discovered in China to cause severe respiratory disease in humans. Since then, over 450 human cases of H7N9 infection have been discovered and 165 of them have died. Multiple epidemiological, phylogenetic, in vivo, and in vitro studies have been done to determine the origin and pathogenesis of novel H7N9 strain. This article reviews the literature related to the epidemiology, evolution, and pathogenesis of the H7N9 strain since its discovery in February 2013 till August 2014. The data available so far indicate that H7N9 was originated by a two-step reassortment process in birds and transmitted to humans through direct contact with live-bird markets. H7N9 is a low-pathogenic avian virus and contains several molecular signatures for adaptation in mammals. The severity of the respiratory disease caused by novel H7N9 virus in humans can be partly attributed to the age, sex, and underlying medical conditions of the patients. A universal influenza vaccine is not available, though several strain-specific H7N9 candidate vaccine viruses have been developed. Further, novel H7N9 virus is resistant to antiviral drug amantadine and some H7N9 isolates have acquired the resistance to neuraminidase-inhibitors. Therefore, constant surveillance and prompt control measures combined with novel research approaches to develop alternative and effective anti-influenza strategies are needed to overcome influenza A virus. Copyright © 2014 Elsevier B.V. All rights reserved.

The impact of H9N2 avian influenza virus vaccine antigenic variation on virus infectious dose in chickens

USDA-ARS?s Scientific Manuscript database

The H9 subtype of avian influenza virus is wide-spread in the areas of Asia and Middle East. Selection of effective vaccines that provide effective protection mainly depends on the antigenic match of the hemagglutinin protein (HA), between the vaccine and the field strain. To determine how the ant...

A Novel Activation Mechanism of Avian Influenza Virus H9N2 by Furin

PubMed Central

Tse, Longping V.; Hamilton, Alice M.; Friling, Tamar

2014-01-01

Avian influenza virus H9N2 is prevalent in waterfowl and has become endemic in poultry in Asia and the Middle East. H9N2 influenza viruses have served as a reservoir of internal genes for other avian influenza viruses that infect humans, and several cases of human infection by H9N2 influenza viruses have indicated its pandemic potential. Fortunately, an extensive surveillance program enables close monitoring of H9N2 influenza viruses worldwide and has generated a large repository of virus sequences and phylogenetic information. Despite the large quantity of sequences in different databases, very little is known about specific virus isolates and their pathogenesis. Here, we characterize a low-pathogenicity avian influenza virus, A/chicken/Israel/810/2001 (H9N2) (Israel810), which is representative of influenza virus strains that have caused severe morbidity and mortality in poultry farms. We show that under certain circumstances the Israel810 hemagglutinin (HA) can be activated by furin, a hallmark of highly pathogenic avian influenza virus. We demonstrate that Israel810 HA can be cleaved in cells with high levels of furin expression and that a mutation that eliminates a glycosylation site in HA1 allows the Israel810 HA to gain universal cleavage in cell culture. Pseudoparticles generated from Israel810 HA, or the glycosylation mutant, transduce cells efficiently. In contrast, introduction of a polybasic cleavage site into Israel810 HA leads to pseudoviruses that are compromised for transduction. Our data indicate a mechanism for an H9N2 evolutionary pathway that may allow it to gain virulence in a distinct manner from H5 and H7 influenza viruses. PMID:24257604

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.

Evaluation of Three Live Attenuated H2 Pandemic Influenza Vaccine Candidates in Mice and Ferrets

PubMed Central

Chen, Grace L.; Lamirande, Elaine W.; Cheng, Xing; Torres-Velez, Fernando; Orandle, Marlene; Jin, Hong; Kemble, George

2014-01-01

ABSTRACT H2 influenza viruses have not circulated in humans since 1968, and therefore a significant portion of the population would be susceptible to infection should H2 influenza viruses reemerge. H2 influenza viruses continue to circulate in avian reservoirs worldwide, and these reservoirs are a potential source from which these viruses could emerge. Three reassortant cold-adapted (ca) H2 pandemic influenza vaccine candidates with hemagglutinin (HA) and neuraminidase (NA) genes derived from the wild-type A/Japan/305/1957 (H2N2) (Jap/57), A/mallard/6750/1978 (H2N2) (mal/78), or A/swine/MO/4296424/2006 (H2N3) (sw/06) viruses and the internal protein gene segments from the A/Ann Arbor/6/60 ca virus were generated by plasmid-based reverse genetics (Jap/57 ca, mal/78 ca, and sw/06 ca, respectively). The vaccine candidates exhibited the in vitro phenotypes of temperature sensitivity and cold adaptation and were restricted in replication in the respiratory tract of ferrets. In mice and ferrets, the vaccines elicited neutralizing antibodies and conferred protection against homologous wild-type virus challenge. Of the three candidates, the sw/06 ca vaccine elicited cross-reactive antibodies and provided significant protection against the greatest number of heterologous viruses. These observations suggest that the sw/06 ca vaccine should be further evaluated in a clinical trial as an H2 pandemic influenza vaccine candidate. IMPORTANCE Influenza pandemics arise when novel influenza viruses are introduced into a population with little prior immunity to the new virus and often result in higher rates of illness and death than annual seasonal influenza epidemics. An influenza H2 subtype virus caused a pandemic in 1957, and H2 viruses circulated in humans till 1968. H2 influenza viruses continue to circulate in birds, and the development of an H2 influenza vaccine candidate is therefore considered a priority in preparing for future pandemics. However, we cannot predict whether a

Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.

PubMed

Belanov, Sergei S; Bychkov, Dmitrii; Benner, Christian; Ripatti, Samuli; Ojala, Teija; Kankainen, Matti; Kai Lee, Hong; Wei-Tze Tang, Julian; Kainov, Denis E

2015-11-27

Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities.

PubMed

To, Kelvin K W; Chan, Jasper F W; Chen, Honglin; Li, Lanjuan; Yuen, Kwok-Yung

2013-09-01

Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with suboptimum biosecurity measures in live poultry markets and farms-predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phylogenetic Diversity and Genotypical Complexity of H9N2 Influenza A Viruses Revealed by Genomic Sequence Analysis

PubMed Central

Dong, Guoying; Luo, Jing; Zhang, Hong; Wang, Chengmin; Duan, Mingxing; Deliberto, Thomas Jude; Nolte, Dale Louis; Ji, Guangju; He, Hongxuan

2011-01-01

H9N2 influenza A viruses have become established worldwide in terrestrial poultry and wild birds, and are occasionally transmitted to mammals including humans and pigs. To comprehensively elucidate the genetic and evolutionary characteristics of H9N2 influenza viruses, we performed a large-scale sequence analysis of 571 viral genomes from the NCBI Influenza Virus Resource Database, representing the spectrum of H9N2 influenza viruses isolated from 1966 to 2009. Our study provides a panoramic framework for better understanding the genesis and evolution of H9N2 influenza viruses, and for describing the history of H9N2 viruses circulating in diverse hosts. Panorama phylogenetic analysis of the eight viral gene segments revealed the complexity and diversity of H9N2 influenza viruses. The 571 H9N2 viral genomes were classified into 74 separate lineages, which had marked host and geographical differences in phylogeny. Panorama genotypical analysis also revealed that H9N2 viruses include at least 98 genotypes, which were further divided according to their HA lineages into seven series (A–G). Phylogenetic analysis of the internal genes showed that H9N2 viruses are closely related to H3, H4, H5, H7, H10, and H14 subtype influenza viruses. Our results indicate that H9N2 viruses have undergone extensive reassortments to generate multiple reassortants and genotypes, suggesting that the continued circulation of multiple genotypical H9N2 viruses throughout the world in diverse hosts has the potential to cause future influenza outbreaks in poultry and epidemics in humans. We propose a nomenclature system for identifying and unifying all lineages and genotypes of H9N2 influenza viruses in order to facilitate international communication on the evolution, ecology and epidemiology of H9N2 influenza viruses. PMID:21386964

Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A(H3N2) strains in Korea

PubMed Central

Park, Sehee; Bae, Joon-Yong; Yoo, Kirim; Cheong, Hee Jin; Noh, Ji Yun; Hong, Kyung Wook; Lemey, Philippe; Vrancken, Bram; Kim, Juwon; Nam, Misun; Yun, Soo-Hyeon; Cho, Woo In; Song, Joon Young; Kim, Woo Joo; Park, Mee Sook; Song, Jin-Won; Kee, Sun-Ho; Song, Ki-Joon; Park, Man-Seong

2017-01-01

Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness. PMID:28257427

H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

PubMed

Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui

2015-12-01

The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

[Results of clinical trials on reactogenicity, safety, and immunogenicity of influenza allantoic intranasal live vaccine "Ultragrivac" (type A/H5N2)].

PubMed

Mazurkova, N A; Ryndiuk, N N; Shishkina, L N; Ternovoĭ, V A; Tumanov, Iu V; Bulychev, L E; Skarnovich, M O; Kabanov, A S; Panchenko, S G; Aleĭnikov, R P; Il'ina, T N; Kuzubov, V I; Mel'nikov, S Ia; Mironov, A N; Korovkin, S A; Sergeev, A N; Drozdov, I G

2010-01-01

Results of phase II of a clinical trial of the influenza allantoic intranasal live vaccine "Ultragrivac" (type A/H5N2) are presented. The vaccine was developed based on strain /17/Duck/Potsdam/86/92 H5N2 [17/H5] - reassortant of two viruses, /Leningrad/134/17/57 (H2N2) and /Duck/Potsdam/1402-86 (H5N2), obtained from the Virology Department, St. Petersburg Institute of Experimental Medicine.Two schemes of immunization (with revaccination on days 10 and 21) were used. Evaluation of vaccine immunogenicity included determination of local, cellular and humoral immunity. A significant rise in the level of secretory IgA in the nasal cavity of vaccinated volunteers (with revaccination on days 10 and 21) was documented after application of the vaccine. The postvaccination humoral immune response was estimated from the level of significant (4-fold and more) antibody seroconversions, geometric mean titers of antibodies to two strains of influenza virus /17/Duck/Potsdam/86/92 H5N2 [17/H5] and /Chicken/Suzdalka/Nov-11/2005 (H5N1), and their incremental rate. Results of measurement of antibody titers in hemagglutination-inhibition assay are presented, with two antigens being used to analyse all serum samples from volunteers twice vaccinated with influenza vaccine "Ultragrivac" at 10 and 21 day intervals. Result of phase II of this clinical study show that influenza allantoic intranasal live vaccine "Ultragrivac" is nonreactogenic and safe for both vaccinated and surrounding individuals. Moreover, it is sufficiently immunogenic with respect not only to homologous virus A(H5N2) but also to the A(H5N1) strain.

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.

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

The replication of Bangladeshi H9N2 avian influenza viruses carrying genes from H7N3 in mammals

PubMed Central

Shanmuganatham, Karthik K; Jones, Jeremy C; Marathe, Bindumadhav M; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Turner, Jasmine; Rabiul Alam, S M; Kamrul Hasan, M; Akhtar, Sharmin; Seiler, Patrick; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2016-01-01

H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans. PMID:27094903

The replication of Bangladeshi H9N2 avian influenza viruses carrying genes from H7N3 in mammals.

PubMed

Shanmuganatham, Karthik K; Jones, Jeremy C; Marathe, Bindumadhav M; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Turner, Jasmine; Rabiul Alam, S M; Kamrul Hasan, M; Akhtar, Sharmin; Seiler, Patrick; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2016-04-20

H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans.

Global alert to avian influenza virus infection: From H5N1 to H7N9

PubMed Central

Poovorawan, Yong; Pyungporn, Sunchai; Prachayangprecha, Slinporn; Makkoch, Jarika

2013-01-01

Outbreak of a novel influenza virus is usually triggered by mutational change due to the process known as ‘antigenic shift’ or re-assortment process that allows animal-to-human or avian-to-human transmission. Birds are a natural reservoir for the influenza virus, and subtypes H5, H7, and H9 have all caused outbreaks of avian influenza in human populations. An especially notorious strain is the HPAI influenza virus H5N1, which has a mortality rate of approximately 60% and which has resulted in numerous hospitalizations, deaths, and significant economic loss. In March 2013, in Eastern China, there was an outbreak of the novel H7N9 influenza virus, which although less pathogenic in avian species, resulted in 131 confirmed cases and 36 deaths in humans over a two-month span. The rapid outbreak of this virus caused global concern but resulted in international cooperation to control the outbreak. Furthermore, cooperation led to valuable research-sharing including genome sequencing of the virus, the development of rapid and specific diagnosis, specimen sharing for future studies, and vaccine development. Although a H7N9 pandemic in the human population is possible due to its rapid transmissibility and extensive surveillance, the closure of the live-bird market will help mitigate the possibility of another H7N9 outbreak. In addition, further research into the source of the outbreak, pathogenicity of the virus, and the development of specific and sensitive detection assays will be essential for controlling and preparing for future H7N9 outbreaks. PMID:23916331

Identification, sequence analysis, and infectivity of H9N2 avian influenza viruses isolated from geese.

PubMed

Zhu, Rui; Yang, Xueqin; Zhang, Jianjun; Xu, Danwen; Fan, Jiawen; Shi, Huoying; Wang, Shifeng; Liu, Xiufan

2018-05-31

The subtype H9N2 avian influenza virus greatly threatens the Chinese poultry industry, even with annual vaccination. Waterfowl can be asymptomatically infected with the H9N2 virus. In this study, three H9N2 virus strains, designated A/Goose/Jiangsu/YZ527/2011 (H9N2, Gs/JS/YZ527/11), A/Goose/Jiangsu/SQ119/2012 (H9N2, Gs/JS/SQ119/12), and A/Goose/Jiangsu/JD564/2012 (H9N2, Gs/JS/JD564/12), were isolated from domestic geese. Molecular characterization of the three isolates showed that the Gs/JS/YZ527/11 virus is a double-reassortant virus, combining genes of A/Quail/Hong Kong/G1/97 (H9N2, G1/97)-like and A/Chicken/Shanghai/F/98 (H9N2, F/98)-like; the Gs/JS/SQ119/12 virus is a triple-reassortant virus combining genes of G1/97-like, F/98-like, and A/Duck/Shantou/163/2004 (H9N2, ST/163/04)-like. The sequences of Gs/JS/JD564/12 share high homology with those of the F/98 virus, except for the neuraminidase gene, whereas the internal genes of Gs/JS/YZ527/11 and Gs/JS/SQ119/12 are closely related to those of the H7N9 viruses. An infectivity analysis of the three isolates showed that Gs/JS/SQ119/12 and Gs/JS/YZ527/11 replicated well, with seroconversion, in geese and chickens, the Gs/JS/JD564/12 did not infect well in geese or chickens, and the F/98 virus only infected chickens, with seroconversion. Emergence of these new reassortant H9N2 avian influenza viruses indicates that these viruses can infect both chicken and goose and can produce different types of lesions in each species.

Identification, sequence analysis, and infectivity of H9N2 avian influenza viruses isolated from geese

PubMed Central

Zhu, Rui; Yang, Xueqin; Zhang, Jianjun; Xu, Danwen; Fan, Jiawen; Wang, Shifeng; Liu, Xiufan

2018-01-01

The subtype H9N2 avian influenza virus greatly threatens the Chinese poultry industry, even with annual vaccination. Waterfowl can be asymptomatically infected with the H9N2 virus. In this study, three H9N2 virus strains, designated A/Goose/Jiangsu/YZ527/2011 (H9N2, Gs/JS/YZ527/11), A/Goose/Jiangsu/SQ119/2012 (H9N2, Gs/JS/SQ119/12), and A/Goose/Jiangsu/JD564/2012 (H9N2, Gs/JS/JD564/12), were isolated from domestic geese. Molecular characterization of the three isolates showed that the Gs/JS/YZ527/11 virus is a double-reassortant virus, combining genes of A/Quail/Hong Kong/G1/97 (H9N2, G1/97)-like and A/Chicken/Shanghai/F/98 (H9N2, F/98)-like; the Gs/JS/SQ119/12 virus is a triple-reassortant virus combining genes of G1/97-like, F/98-like, and A/Duck/Shantou/163/2004 (H9N2, ST/163/04)-like. The sequences of Gs/JS/JD564/12 share high homology with those of the F/98 virus, except for the neuraminidase gene, whereas the internal genes of Gs/JS/YZ527/11 and Gs/JS/SQ119/12 are closely related to those of the H7N9 viruses. An infectivity analysis of the three isolates showed that Gs/JS/SQ119/12 and Gs/JS/YZ527/11 replicated well, with seroconversion, in geese and chickens, the Gs/JS/JD564/12 did not infect well in geese or chickens, and the F/98 virus only infected chickens, with seroconversion. Emergence of these new reassortant H9N2 avian influenza viruses indicates that these viruses can infect both chicken and goose and can produce different types of lesions in each species. PMID:29366299

The Continuing Evolution of H5N1 and H9N2 Influenza Viruses in Bangladesh

PubMed Central

Marinova-Petkova, Atanaska; Shanmuganatham, Karthik; Feeroz, Mohammed M.; Jones-Engel, Lisa; Hassan, M. Kamrul; Akhtar, Sharmin; Turner, Jasmine; Walker, David; Seiler, Patrick; Franks, John; McKenzie, Pamela; Krauss, Scott; Webby, Richard J.; Webster, Robert G.

2017-01-01

Summary In 2011, avian influenza surveillance at the Bangladesh live bird markets (LBMs) showed complete replacement of the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.2.2 (Qinghai-like H5N1 lineage) by the HPAI H5N1 clade 2.3.2.1. This clade, which continues to circulate in Bangladesh and neighboring countries, is an intra- and inter-clade reassortant; its HA, PB1, PA and NS genes come from subclade 2.3.2.1a; PB2 from subclade 2.3.2.1c; and NA, NP, and M from clade 2.3.4.2. The H9N2 influenza viruses co-circulating in the Bangladesh LBMs are also reassortants, possessing five genes (NS, M, NP, PA, and PB1) from a HPAI H7N3 virus previously isolated in Pakistan. Despite frequent co-infection of chickens and ducks, reassortment between these H5N1 and H9N2 viruses has been rare. However, all such reassortants detected in 2011 through 2013 have carried 7 genes from HPAI H5N1 clade 2.3.2.1a and the PB1 gene from the Bangladeshi H9N2 clade G1 Mideast, itself derived from HPAI H7N3 virus. Although, the live birds which we sampled in Bangladesh showed no clinical signs of morbidity, the emergence of this reassortant HPAI H5N1 lineage further complicates endemic circulation of H5N1 viruses in Bangladesh, posing a threat to both poultry and humans. PMID:27309046

Enhanced humoural and cellular immune responses to influenza H7N9 antigen HA1-2 fused with flagellin in chickens.

PubMed

Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

2017-06-21

Sudden increases in the number of human A (H7N9) cases reported during December and January have been observed in previous years. Most reported infection cases are due to prior exposure to live poultry or potentially contaminated environments. Low pathogenicity of influenza A (H7N9) virus in avian species complicates timely discovery of infected birds. Therefore, there is a pressing need to develop safe and effective anti-H7N9 vaccines for poultry to reduce the risk of human infection and prevent the emergence of novel mutated strains. In addition to a good antigen, an effective vaccine also requires an appropriate adjuvant to enhance its immunogenicity. Previously, we generated an H7N9 influenza recombinant subunit vaccine (HA1-2-fliC), in which haemagglutinin globular head domain (HA1-2) was fused with flagellin (fliC), a potent TLR5 ligand, and demonstrated that HA1-2-fliC elicited effective HA1-2-specific immune responses in mice. In this study, we determined flagellin-induced expression profiles of cytokines and chemokines in different types of avian immune cells in vitro and ex vivo. We found that flagellin significantly increased the expression levels of CXCL inflammatory chemokines (CXCLi1 and CXCLi2) and CCL chemokines (MIP-1β and MCP-3) in avian macrophage HD11 cells. In addition, HA1-2-fliC induced significant upregulation of cytokines (IL-1β, IL-6, IL-18 and IFN-γ) and chemokines (CXCLi1, CXCLi2 and MIP-1β) in ex vivo splenic lymphocytes and peripheral blood mononuclear cells (PBMCs), suggesting that flagellin promoted immune responses of avian cells in vitro. We also evaluated specific humoural and cellular immune responses induced by HA1-2-fliC and found that chickens immunised intramuscularly with HA1-2-fliC showed significantly higher HA1-2-specific immunoglobulin (Ig)G titers in serum. Furthermore, HA1-2-fliC potentiated cellular immune responses, as reflected by an increase in CD4 + and CD8 + T cells and proliferation of PBMCs. Significantly

Willingness to accept H1N1 pandemic influenza vaccine: a cross-sectional study of Hong Kong community nurses.

PubMed

Wong, Samuel Y S; Wong, Eliza L Y; Chor, Josette; Kung, Kenny; Chan, Paul K S; Wong, Carmen; Griffiths, Sian M

2010-10-29

The 2009 pandemic of influenza A (H1N1) infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1) infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS) in Hong Kong on their acceptance of influenza A (H1N1) influenza vaccination. 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1) vaccine were analyzed. Twenty-seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1) vaccination (OR = 4.03; 95% CI: 2.03-7.98). Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1) vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1) vaccination to protect vulnerable patient populations is needed.

Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

PubMed

Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

2017-10-01

Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

[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

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

Standardization of inactivated H5N2 influenza vaccine and efficacy against lethal A/Chicken/Pennsylvania/1370/83 infection.

PubMed

Wood, J M; Kawaoka, Y; Newberry, L A; Bordwell, E; Webster, R G

1985-01-01

The hemagglutinin concentration of beta-propiolactone-inactivated influenza vaccine containing A/Duck/N.Y./189/82 (H5N2) virus was measured by single-radial-immunodiffusion (SRD) test. After administration of vaccine to chickens in Freund's complete adjuvant, vaccine efficacy was assessed by challenge with lethal A/Chicken/Penn./1370/83 (H5N2) virus. SRD potency values correlated with post-vaccination antibody levels and protection against infection.

Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam.

PubMed

Takemae, Nobuhiro; Nguyen, Tung; Ngo, Long Thanh; Hiromoto, Yasuaki; Uchida, Yuko; Pham, Vu Phong; Kageyama, Tsutomu; Kasuo, Shizuko; Shimada, Shinichi; Yamashita, Yasutaka; Goto, Kaoru; Kubo, Hideyuki; Le, Vu Tri; Van Vo, Hung; Do, Hoa Thi; Nguyen, Dang Hoang; Hayashi, Tsuyoshi; Matsuu, Aya; Saito, Takehiko

2013-04-01

The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.

Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees

PubMed Central

2013-01-01

Background The efficacy of the H1N1 influenza vaccine relies on the induction of both humoral and cellular responses. This study evaluated the humoral and cellular responses to a monovalent non-adjuvanted pandemic influenza A/H1N1 vaccine in occupationally exposed subjects who were previously vaccinated with a seasonal vaccine. Methods Sixty healthy workers from a respiratory disease hospital were recruited. Sera and peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 month after vaccination with a non-adjuvanted monovalent 2009 H1N1 vaccine (Influenza A (H1N1) 2009 Monovalent Vaccine Panenza, Sanofi Pasteur). Antibody titers against the pandemic A/H1N1 influenza virus were measured via hemagglutination inhibition (HI) and microneutralization assays. Antibodies against the seasonal HA1 were assessed by ELISA. The frequency of IFN-γ-producing cells as well as CD4+ and CD8+ T cell proliferation specific to the pandemic virus A/H1N peptides, seasonal H1N1 peptides and seasonal H3N2 peptides were assessed using ELISPOT and flow cytometry. Results At baseline, 6.7% of the subjects had seroprotective antibody titers. The seroconversion rate was 48.3%, and the seroprotection rate was 66.7%. The geometric mean titers (GMTs) were significantly increased (from 6.8 to 64.9, p < 0.05). Forty-nine percent of the subjects had basal levels of specific IFN-γ-producing T cells to the pandemic A/H1N1 peptides that were unchanged post-vaccination. CD4+ T cell proliferation in response to specific pandemic A/H1N1 virus peptides was also unchanged; in contrast, the antigen-specific proliferation of CD8+ T cells significantly increased post-vaccination. Conclusion Our results indicate that a cellular immune response that is cross-reactive to pandemic influenza antigens may be present in populations exposed to the circulating seasonal influenza virus prior to pandemic or seasonal vaccination. Additionally, we found that the pandemic vaccine induced a

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

In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

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

Ebrahimi, Seyyed Mahmoud, E-mail: smebrahimi@shirazu.ac.ir; Research Center of Virus and Vaccine, Baqiyatallah University of Medical Science, P.O.Box 14155-3651, Tehran; Dabaghian, Mehran

Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2more » (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.« less

Detection of avian H7N9 influenza A viruses at the Yangtze Delta Region of China during early H7N9 outbreaks

PubMed Central

Li, Yin; Huang, Xin-mei; Zhao, Dong-min; Liu, Yu-zhuo; He, Kong-wang; Liu, Yao-xing; Chen, Chang-hai; Long, Li-Ping; Xu, Yifei; Xie, Xing-xing; Han, Kai-kai; Liu, Xiao-yan; Yang, Jing; Zhang, You-Fa; Fan, Feng; Webby, Richard; Wan, Xiu-Feng

2016-01-01

SUMMARY Since the first H7N9 human case in Shanghai, February 19, 2013, the emerging avian-origin H7N9 influenza A virus has become an epizootic virus in China, posing a potential pandemic threat to public health. From April 2 to April 28, 2013, 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (LPMs) and 13 backyard poultry farms (BPFs) across three cities, Wuxi, Suzhou, and Nanjing, in the Yangtze Delta Region. A total of 22 isolates were recovered, and 6 were subtyped as H7N9, 9 as H9N2, 4 as H7N9/H9N2, and 3 un-subtyped influenza A viruses. Genomic sequences showed that the HA and NA genes of the H7N9 viruses were similar to those of the H7N9 human isolates as well as other avian origin H7N9 isolates in the region but the PB1, PA, NP, and MP genes of the sequenced viruses were, however, more diverse. Among the four H7N9/H9N2 mixed infections, three were from LPM whereas the other one from the ducks at one BPF, which were H7N9 negative in serological analyses. A survey of the bird trading records of the LPMs and BPFs indicates that trading was a likely route for virus transmission across these regions. Our results suggested that a better biosecurity and more effective vaccination should be implemented in backyard farms besides biosecurity management in LPMs. PMID:27309047

75 FR 10268 - Pandemic Influenza Vaccines-Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Pandemic Influenza Vaccines... Preparedness Act for H5N1, H2, H6, H7, H9 and 2009-H1N1 Vaccines: Whereas there are or may be multiple animal... through February 28, 2010 for vaccines against influenza virus strains named in the Declaration other than...

Detection of Avian H7N9 Influenza A Viruses in the Yangtze Delta Region of China During Early H7N9 Outbreaks.

PubMed

Li, Yin; Huang, Xin-Mei; Zhao, Dong-Min; Liu, Yu-Zhuo; He, Kong-Wang; Liu, Yao-Xing; Chen, Chang-Hai; Long, Li-Ping; Xu, Yifei; Xie, Xing-Xing; Han, Kai-Kai; Liu, Xiao-Yan; Yang, Jing; Zhang, You-Fa; Fan, Feng; Webby, Richard; Wan, Xiu-Feng

2016-05-01

Since the first H7N9 human case in Shanghai, February 19, 2013, the emerging avian-origin H7N9 influenza A virus has become an epizootic virus in China, posing a potential pandemic threat to public health. From April 2 to April 28, 2013, some 422 oral-pharyngeal and cloacal swabs were collected from birds and environmental surfaces at five live poultry markets (LPMs) and 13 backyard poultry farms (BPFs) across three cities, Wuxi, Suzhou, and Nanjing, in the Yangtze Delta region. In total 22 isolates were recovered, and six were subtyped as H7N9, nine as H9N2, four as H7N9/H9N2, and three unsubtyped influenza A viruses. Genomic sequences showed that the HA and NA genes of the H7N9 viruses were similar to those of the H7N9 human isolates, as well as other avian-origin H7N9 isolates in the region, but the PB1, PA, NP, and MP genes of the sequenced viruses were more diverse. Among the four H7N9/H9N2 mixed infections, three were from LPM, whereas the other one was from the ducks at one BPF, which were H7N9 negative in serologic analyses. A survey of the bird trading records of the LPMs and BPFs indicates that trading was a likely route for virus transmission across these regions. Our results suggested that better biosecurity and more effective vaccination should be implemented in backyard farms, in addition to biosecurity management in LPMs.

Infectivity and Transmissibility of Avian H9N2 Influenza Viruses in Pigs

PubMed Central

Wang, Jia; Wu, Maocai; Hong, Wenshan; Fan, Xiaohui; Chen, Rirong; Zheng, Zuoyi; Zeng, Yu; Huang, Ren; Zhang, Yu; Lam, Tommy Tsan-Yuk; Smith, David K.

2016-01-01

ABSTRACT The H9N2 influenza viruses that are enzootic in terrestrial poultry in China pose a persistent pandemic threat to humans. To investigate whether the continuous circulation and adaptation of these viruses in terrestrial poultry increased their infectivity to pigs, we conducted a serological survey in pig herds with H9N2 viruses selected from the aquatic avian gene pool (Y439 lineage) and the enzootic terrestrial poultry viruses (G1 and Y280 lineages). We also compared the infectivity and transmissibility of these viruses in pigs. It was found that more than 15% of the pigs sampled from 2010 to 2012 in southern China were seropositive to either G1 or Y280 lineage viruses, but none of the sera were positive to the H9 viruses from the Y439 lineage. Viruses of the G1 and Y280 lineages were able to infect experimental pigs, with detectable nasal shedding of the viruses and seroconversion, whereas viruses of the Y439 lineage did not cause a productive infection in pigs. Thus, adaptation and prevalence in terrestrial poultry could lead to interspecies transmission of H9N2 viruses from birds to pigs. Although H9N2 viruses do not appear to be continuously transmissible among pigs, repeated introductions of H9 viruses to pigs naturally increase the risk of generating mammalian-adapted or reassorted variants that are potentially infectious to humans. This study highlights the importance of monitoring the activity of H9N2 viruses in terrestrial poultry and pigs. IMPORTANCE H9N2 subtype of influenza viruses has repeatedly been introduced into mammalian hosts, including humans and pigs, so awareness of their activity and evolution is important for influenza pandemic preparedness. However, since H9N2 viruses usually cause mild or even asymptomatic infections in mammalian hosts, they may be overlooked in influenza surveillance. Here, we found that the H9N2 viruses established in terrestrial poultry had higher infectivity in pigs than those from aquatic birds, which

Infectivity and Transmissibility of Avian H9N2 Influenza Viruses in Pigs.

PubMed

Wang, Jia; Wu, Maocai; Hong, Wenshan; Fan, Xiaohui; Chen, Rirong; Zheng, Zuoyi; Zeng, Yu; Huang, Ren; Zhang, Yu; Lam, Tommy Tsan-Yuk; Smith, David K; Zhu, Huachen; Guan, Yi

2016-01-13

The H9N2 influenza viruses that are enzootic in terrestrial poultry in China pose a persistent pandemic threat to humans. To investigate whether the continuous circulation and adaptation of these viruses in terrestrial poultry increased their infectivity to pigs, we conducted a serological survey in pig herds with H9N2 viruses selected from the aquatic avian gene pool (Y439 lineage) and the enzootic terrestrial poultry viruses (G1 and Y280 lineages). We also compared the infectivity and transmissibility of these viruses in pigs. It was found that more than 15% of the pigs sampled from 2010 to 2012 in southern China were seropositive to either G1 or Y280 lineage viruses, but none of the sera were positive to the H9 viruses from the Y439 lineage. Viruses of the G1 and Y280 lineages were able to infect experimental pigs, with detectable nasal shedding of the viruses and seroconversion, whereas viruses of the Y439 lineage did not cause a productive infection in pigs. Thus, adaptation and prevalence in terrestrial poultry could lead to interspecies transmission of H9N2 viruses from birds to pigs. Although H9N2 viruses do not appear to be continuously transmissible among pigs, repeated introductions of H9 viruses to pigs naturally increase the risk of generating mammalian-adapted or reassorted variants that are potentially infectious to humans. This study highlights the importance of monitoring the activity of H9N2 viruses in terrestrial poultry and pigs. H9N2 subtype of influenza viruses has repeatedly been introduced into mammalian hosts, including humans and pigs, so awareness of their activity and evolution is important for influenza pandemic preparedness. However, since H9N2 viruses usually cause mild or even asymptomatic infections in mammalian hosts, they may be overlooked in influenza surveillance. Here, we found that the H9N2 viruses established in terrestrial poultry had higher infectivity in pigs than those from aquatic birds, which suggests that adaptation of

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.

Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape.

PubMed

Peacock, Thomas; Reddy, Kolli; James, Joe; Adamiak, Beata; Barclay, Wendy; Shelton, Holly; Iqbal, Munir

2016-01-07

H9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants. To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2 viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique 'escape' mutants with substitutions across nine different amino acid residues in hemagglutinin including seven that have not been described as antigenic determinants for H9N2 viruses before. Competition assays and structural mapping revealed two novel, discrete antigenic sites "H9-A" and "H9-B". Additionally, a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and vaccine design.

Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape

PubMed Central

Peacock, Thomas; Reddy, Kolli; James, Joe; Adamiak, Beata; Barclay, Wendy; Shelton, Holly; Iqbal, Munir

2016-01-01

H9N2 avian influenza virus is a major cause of poultry production loss across Asia leading to the wide use of vaccines. Efficacy of vaccines is often compromised due to the rapid emergence of antigenic variants. To improve the effectiveness of vaccines in the field, a better understanding of the antigenic epitopes of the major antigen, hemagglutinin, is required. To address this, a panel of nine monoclonal antibodies were generated against a contemporary Pakistani H9N2 isolate, which represents a major Asian H9N2 viral lineage. Antibodies were characterized in detail and used to select a total of 26 unique ‘escape’ mutants with substitutions across nine different amino acid residues in hemagglutinin including seven that have not been described as antigenic determinants for H9N2 viruses before. Competition assays and structural mapping revealed two novel, discrete antigenic sites “H9-A” and “H9-B”. Additionally, a second subset of escape mutants contained amino acid deletions within the hemagglutinin receptor binding site. This constitutes a novel method of escape for group 1 hemagglutinins and could represent an alternative means for H9N2 viruses to overcome vaccine induced immunity. These results will guide surveillance efforts for arising antigenic variants as well as evidence based vaccine seed selection and vaccine design. PMID:26738561

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

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.

Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014.

PubMed

Thuy, Duong Mai; Peacock, Thomas P; Bich, Vu Thi Ngoc; Fabrizio, Thomas; Hoang, Dang Nguyen; Tho, Nguyen Dang; Diep, Nguyen Thi; Nguyen, Minh; Hoa, Le Nguyen Minh; Trang, Hau Thi Thu; Choisy, Marc; Inui, Ken; Newman, Scott; Trung, Nguyen Vu; van Doorn, Rogier; To, Thanh Long; Iqbal, Munir; Bryant, Juliet E

2016-10-01

Despite their classification as low pathogenicity avian influenza viruses (LPAIV), A/H9N2 viruses cause significant losses in poultry in many countries throughout Asia, the Middle East and North Africa. To date, poultry surveillance in Vietnam has focused on detection of influenza H5 viruses, and there is limited understanding of influenza H9 epidemiology and transmission dynamics. We determined prevalence and diversity of influenza A viruses in chickens from live bird markets (LBM) of 7 northern Vietnamese provinces, using pooled oropharyngeal swabs collected from October to December 2014. Screening by real time RT-PCR revealed 1207/4900 (24.6%) of pooled swabs to be influenza A virus positive; overall prevalence estimates after accounting for pooling (5 swabs/pools) were 5.8% (CI 5.4-6.0). Subtyping was performed on 468 pooled swabs with M gene Ct<26. No influenza H7 was detected; 422 (90.1%) were H9 positive; and 22 (4.7%) were H5 positive. There was no evidence was of interaction between H9 and H5 virus detection rates. We sequenced 17 whole genomes of A/H9N2, 2 of A/H5N6, and 11 partial genomes. All H9N2 viruses had internal genes that clustered with genotype 57 and were closely related to Chinese human isolates of A/H7N9 and A/H10N8. Using a nucleotide divergence cutoff of 98%, we identified 9 distinct H9 genotypes. Phylogenetic analysis suggested multiple introductions of H9 viruses to northern Vietnam rather than in-situ transmission. Further investigations of H9 prevalence and diversity in other regions of Vietnam are warranted to assess H9 endemicity elsewhere in the country. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Antigenic and Molecular Characterization of Avian Influenza A(H9N2) Viruses, Bangladesh

PubMed Central

Shanmuganatham, Karthik; Feeroz, Mohammed M.; Jones-Engel, Lisa; Smith, Gavin J.D.; Fourment, Mathieu; Walker, David; McClenaghan, Laura; Alam, S.M. Rabiul; Hasan, M. Kamrul; Seiler, Patrick; Franks, John; Danner, Angie; Barman, Subrata; McKenzie, Pamela; Krauss, Scott; Webby, Richard J.

2013-01-01

Human infection with avian influenza A(H9N2) virus was identified in Bangladesh in 2011. Surveillance for influenza viruses in apparently healthy poultry in live-bird markets in Bangladesh during 2008–2011 showed that subtype H9N2 viruses are isolated year-round, whereas highly pathogenic subtype H5N1 viruses are co-isolated with subtype H9N2 primarily during the winter months. Phylogenetic analysis of the subtype H9N2 viruses showed that they are reassortants possessing 3 gene segments related to subtype H7N3; the remaining gene segments were from the subtype H9N2 G1 clade. We detected no reassortment with subtype H5N1 viruses. Serologic analyses of subtype H9N2 viruses from chickens revealed antigenic conservation, whereas analyses of viruses from quail showed antigenic drift. Molecular analysis showed that multiple mammalian-specific mutations have become fixed in the subtype H9N2 viruses, including changes in the hemagglutinin, matrix, and polymerase proteins. Our results indicate that these viruses could mutate to be transmissible from birds to mammals, including humans. PMID:23968540

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

H9N2 low pathogenic avian influenza in Pakistan (2012-2015)

USDA-ARS?s Scientific Manuscript database

Significant economic losses from deaths and decreased egg production have resulted from H9N2 low pathogenic avian influenza virus (LPAIV) infections in poultry across North Africa, the Middle East and Asia. The H9N2 LPAIVs have been endemic in Pakistani poultry since 1996, but no new viruses have be...

H9N2 influenza virus isolated from minks has enhanced virulence in mice.

PubMed

Xue, R; Tian, Y; Hou, T; Bao, D; Chen, H; Teng, Q; Yang, J; Li, X; Wang, G; Li, Z; Liu, Q

2018-06-01

H9N2 is one of the major subtypes of influenza virus circulating in poultry in China, which has a wide host range from bird to mammals. Two H9N2 viruses were isolated from one mink farm in 2014. Phylogenetic analysis showed that internal genes of the H9N2 viruses have close relationship with those of H7N9 viruses. Interestingly, two H9N2 were separated in phylogenetic trees, indicating that they are introduced to this mink farm in two independent events. And further mice studies showed that one H9N2 caused obvious weight loss and 20% mortality in infected mice, while another virus did not cause any clinical sign in mice infected at the same dose. Genetic analysis indicated that the virulent H9N2 contain a natural mutation at 701N in PB2 protein, which was reported to contribute to mammalian adaptation. However, such substitution is absent in the H9N2 avirulent to mice. Circulation of H9N2 in mink may drive the virus to adapt mammals; continual surveillance of influenza virus in mink was warranted. © 2018 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

CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

PubMed Central

Qin, Tao; Yin, Yinyan; Yu, Qinghua; Huang, Lulu; Wang, Xiaoqing; Lin, Jian

2015-01-01

ABSTRACT The spread of the low-pathogenicity avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, the mucosal barrier seems to be a major factor hampering its development. CpG oligodeoxynucleotides, a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpGs to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpGs provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs) and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103+ DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DC recruitment and TED formation. Virus-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpGs was independent of direct epithelial transport via the transcellular or paracellular pathway. Taken together, our data demonstrated that CpGs enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for optimal adaptive immune responses. IMPORTANCE This paper demonstrates by both an in vivo and an in vitro coculture model that CpG oligodeoxynucleotides, known as an adjuvant generally targeting downstream immune responses, also are crucial for the transport of H9N2 WIV across nasal epithelial cells (ECs) via the uptake of transepithelial dendrites (TEDs). Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpGs is based on strengthening the transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the

Interim estimates of divergence date and vaccine strain match of human influenza A(H3N2) virus from systematic influenza surveillance (2010-2015) in Hangzhou, southeast of China.

PubMed

Li, Jun; Zhou, Yin-yan; Kou, Yu; Yu, Xin-fen; Zheng, Zhi-bei; Yang, Xu-hui; Wang, Hao-qiu

2015-11-01

In the post-pandemic period 2010-2015, seasonal influenza A(H3N2) virus predominated in Hangzhou, southeast of China, with an increased activity and semi-annual seasons. This study utilized HA virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza A(H3N2) virus from systematic influenza surveillance in Hangzhou. Virological and serological analyses of 124 representative A(H3N2) viruses from prospective studies of systematic surveillance samples were conducted to quantify the genetic and antigenic characteristics and their vaccine strain match. Bayesian phylogenetic inference showed that two separate subgroups 3C.3 and 3C.2 probably diverged from group 3C in early 2012 and then evolved into groups 3C.3a and 3C.2a, respectively, in the 2014/15 influenza season. Furthermore, high amino acid substitution rates of the HA1 subunit were found in A(H3N2) group 3C.2a variants, indicating that increased antigenic drift of A(H3N2) group 3C.2a virus is associated with a vaccine mismatch to the 2015/16 vaccine reference strain Switzerland/9715293/2013 (group 3C.3a). A portion of the group 3C.2a isolates are not covered by the current A(H3N2) vaccine strain. These findings offer insights into the emergence of group 3C.2a variants with epidemic potential in the imminent influenza seasons. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Genesis of avian influenza H9N2 in Bangladesh.

PubMed

Shanmuganatham, Karthik; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Alam, SMRabiul; Hasan, MKamrul; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2014-12-01

Avian influenza subtype H9N2 is endemic in many bird species in Asia and the Middle East and has contributed to the genesis of H5N1, H7N9 and H10N8, which are potential pandemic threats. H9N2 viruses that have spread to Bangladesh have acquired multiple gene segments from highly pathogenic (HP) H7N3 viruses that are presumably in Pakistan and currently cocirculate with HP H5N1. However, the source and geographic origin of these H9N2 viruses are not clear. We characterized the complete genetic sequences of 37 Bangladeshi H9N2 viruses isolated in 2011-2013 and investigated their inter- and intrasubtypic genetic diversities by tracing their genesis in relationship to other H9N2 viruses isolated from neighboring countries. H9N2 viruses in Bangladesh are homogenous with several mammalian host-specific markers and are a new H9N2 sublineage wherein the hemagglutinin (HA) gene is derived from an Iranian H9N2 lineage (Mideast_B Iran), the neuraminidase (NA) and polymerase basic 2 (PB2) genes are from Dubai H9N2 (Mideast_C Dubai), and the non-structural protein (NS), nucleoprotein (NP), matrix protein (MP), polymerase acidic (PA) and polymerase basic 1 (PB1) genes are from HP H7N3 originating from Pakistan. Different H9N2 genotypes that were replaced in 2006 and 2009 by other reassortants have been detected in Bangladesh. Phylogenetic and molecular analyses suggest that the current genotype descended from the prototypical H9N2 lineage (G1), which circulated in poultry in China during the late 1990s and came to Bangladesh via the poultry trade within the Middle East, and that this genotype subsequently reassorted with H7N3 and H9N2 lineages from Pakistan and spread throughout India. Thus, continual surveillance of Bangladeshi HP H5N1, H7N3 and H9N2 is warranted to identify further evolution and adaptation to humans.

Genesis of avian influenza H9N2 in Bangladesh

PubMed Central

Shanmuganatham, Karthik; Feeroz, Mohammed M; Jones-Engel, Lisa; Walker, David; Alam, SMRabiul; Hasan, MKamrul; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G

2014-01-01

Avian influenza subtype H9N2 is endemic in many bird species in Asia and the Middle East and has contributed to the genesis of H5N1, H7N9 and H10N8, which are potential pandemic threats. H9N2 viruses that have spread to Bangladesh have acquired multiple gene segments from highly pathogenic (HP) H7N3 viruses that are presumably in Pakistan and currently cocirculate with HP H5N1. However, the source and geographic origin of these H9N2 viruses are not clear. We characterized the complete genetic sequences of 37 Bangladeshi H9N2 viruses isolated in 2011–2013 and investigated their inter- and intrasubtypic genetic diversities by tracing their genesis in relationship to other H9N2 viruses isolated from neighboring countries. H9N2 viruses in Bangladesh are homogenous with several mammalian host-specific markers and are a new H9N2 sublineage wherein the hemagglutinin (HA) gene is derived from an Iranian H9N2 lineage (Mideast_B Iran), the neuraminidase (NA) and polymerase basic 2 (PB2) genes are from Dubai H9N2 (Mideast_C Dubai), and the non-structural protein (NS), nucleoprotein (NP), matrix protein (MP), polymerase acidic (PA) and polymerase basic 1 (PB1) genes are from HP H7N3 originating from Pakistan. Different H9N2 genotypes that were replaced in 2006 and 2009 by other reassortants have been detected in Bangladesh. Phylogenetic and molecular analyses suggest that the current genotype descended from the prototypical H9N2 lineage (G1), which circulated in poultry in China during the late 1990s and came to Bangladesh via the poultry trade within the Middle East, and that this genotype subsequently reassorted with H7N3 and H9N2 lineages from Pakistan and spread throughout India. Thus, continual surveillance of Bangladeshi HP H5N1, H7N3 and H9N2 is warranted to identify further evolution and adaptation to humans. PMID:26038507

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.

Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1.

PubMed

Torun, Sebahat D; Torun, Fuat; Catak, Binali

2010-10-10

Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination is necessary. Efforts for orienting

Healthcare workers as parents: attitudes toward vaccinating their children against pandemic influenza A/H1N1

PubMed Central

2010-01-01

Background Both the health care workers (HCWs) and children are target groups for pandemic influenza vaccination. The coverage of the target populations is an important determinant for impact of mass vaccination. The objective of this study is to determine the attitudes of HCWs as parents, toward vaccinating their children with pandemic influenza A/H1N1 vaccine. Methods A cross-sectional questionnaire survey was conducted with health care workers (HCWs) in a public hospital during December 2009 in Istanbul. All persons employed in the hospital with or without a health-care occupation are accepted as HCW. The HCWs who are parents of children 6 months to 18 years of age were included in the study. Pearson's chi-square test and logistic regression analysis was applied for the statistical analyses. Results A total of 389 HCWs who were parents of children aged 6 months-18 years participated study. Among all participants 27.0% (n = 105) reported that themselves had been vaccinated against pandemic influenza A/H1N1. Two third (66.1%) of the parents answered that they will not vaccinate their children, 21.1% already vaccinated and 12.9% were still undecided. Concern about side effect was most reported reason among who had been not vaccinated their children and among undecided parents. The second reason for refusing the pandemic vaccine was concerns efficacy of the vaccine. Media was the only source of information about pandemic influenza in nearly one third of HCWs. Agreement with vaccine safety, self receipt of pandemic influenza A/H1N1 vaccine, and trust in Ministry of Health were found to be associated with the positive attitude toward vaccinating their children against pandemic influenza A/H1N1. Conclusions Persuading parents to accept a new vaccine seems not be easy even if they are HCWs. In order to overcome the barriers among HCWs related to pandemic vaccines, determination of their misinformation, attitudes and behaviors regarding the pandemic influenza vaccination

A Candidate H1N1 Pandemic Influenza Vaccine Elicits Protective Immunity in Mice

PubMed Central

Steitz, Julia; Barlow, Peter G.; Hossain, Jaber; Kim, Eun; Okada, Kaori; Kenniston, Tom; Rea, Sheri; Donis, Ruben O.; Gambotto, Andrea

2010-01-01

Background In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model. Methods We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNγ Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus. Conclusions/Significance A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization. PMID:20463955

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

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

Boonsathorn, Naphatsawan; Panthong, Sumolrat; Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development

Highlights: • A human monoclonal antibody against influenza virus was produced from a volunteer. • The antibody was generated from the PBMCs of the volunteer using the fusion method. • The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). • The antibody targeted a novel epitope in globular head region of the hemagglutinin. • Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutininmore » (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.« less

Protection of chickens against H9N2 avian influenza virus challenge with recombinant Lactobacillus plantarum expressing conserved antigens.

PubMed

Yang, Wen-Tao; Yang, Gui-Lian; Shi, Shao-Hua; Liu, Yu-Ying; Huang, Hai-Bin; Jiang, Yan-Long; Wang, Jian-Zhong; Shi, Chun-Wei; Jing, Yu-Bei; Wang, Chun-Feng

2017-06-01

Avian influenza virus (AIV) is spreading worldwide and is a serious threat to the health of poultry and humans. In many countries, low pathogenic AIVs, such as H9N2, have become an enormous economic burden on the commercial poultry industry because they cause mild respiratory disease and decrease egg production. A recombinant Lactobacillus plantarum NC8 strain expressing NP-M1-DCpep from H9N2 AIV has been studied in a mouse model. However, it remains unknown whether this L. plantarum strain can induce an immune response and provide protection against H9N2 AIV in chickens. In this study, chickens that were orally vaccinated with NC8-pSIP409-NP-M1-DCpep exhibited significantly increased T cell-mediated immune responses and mucosal sIgA and IgG levels, which provided protection against H9N2 AIV challenge. More importantly, compared with oral administration of NC8-pSIP409-NP-M1-DCpep, intranasal administration induced stronger immune responses and provided effective protection against challenge with the H9N2 virus by reducing body weight loss, lung virus titers, and throat pathology. Taken together, these findings suggest that L. plantarum expressing NP-M1-DCpep has potential as a vaccine to combat H9N2 AIV infection.

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