Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection

Prabhu, Nayana; Prabakaran, Mookkan; Ho, Henry Sun Sien; Velumani, Sumathy; Jia, Qiang; Goutama, Michael; Kwang, Jimmy

doi:10.1128/jvi.02165-08

Cited by 109 publications

(83 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That an HPAI H5N1 strain with enhanced transmissibility among humans can be generated in the laboratory is also being debated as a potential new threat, in addition to those represented by natural outbreaks (29). Efforts to develop such universal vaccines encompass a wide range of aspects, including the identification of previously unknown conserved regions or T cell epitopes and new antibodies with broad reactivity that, in turn, could expedite the development of new and more effective strategies (11,13,16,24,28,35,38,41). In addition, extensive studies of the humoral and cell-mediated immunity responsible for inducing cross-protection are being carried out (3,33).…”

mentioning

confidence: 99%

Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Jang

Byun

Lee

et al. 2012

J Virol

View full text Add to dashboard Cite

The rapid transmission of the pandemic 2009 H1N1 influenza virus (pH1N1) among humans has raised the concern of a potential emergence of reassortment between pH1N1 and highly pathogenic influenza strains, especially the avian H5N1 influenza virus. Here, we report that the cold-adapted pH1N1 live attenuated vaccine (CApH1N1) elicits cross-reactive immunity to seasonal and H5 influenza A viruses in the mouse model. Immunization with CApH1N1 induced both systemic and mucosal antibodies with broad reactivity to seasonal and H5 strains, including HAPI H5N1 and the avian H5N2 virus, providing complete protection against heterologous and heterosubtypic lethal challenges. Our results not only accentuate the merit of using live attenuated influenza virus vaccines in view of cross-reactivity but also represent the potential of CApH1N1 live vaccine for mitigating the clinical severity of infections that arise from reassortments between pH1N1 and highly pathogenic H5 subtype viruses.

show abstract

mentioning

confidence: 99%

Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Jang

Byun

Lee

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…During recent decades, many approaches have been investigated to develop new vaccines that offer broad cross-protection as well as convenient preparation and administration. In particular, studies have been conducted to induce cross-protection using M2e (42)(43)(44)(45) and HA2 (9,30,46,47). Considering these observations, we hypothesized that a fusion vaccine based on sM2 and HA2 (sM2HA2) would confer significant cross-protection.…”

Section: Discussionmentioning

confidence: 99%

“…Influenza matrix protein 2 (M2), particularly the ectodomain (M2e), is well conserved across influenza (7) strains and is considered an attractive target for inducing crossprotection against influenza A subtypes. Similarly, the stalk domain, especially the fusion peptide (HA2) of hemagglutinin (HA), is another potent conserved region (8) that can induce a specific Ab response with cross-protection within a given subtype and even among various subtypes of influenza A virus (9). However, the drawback of these M2-and HA2-based vaccines is their low immunogenicity, which can reduce mortality but not morbidity in animal tests.…”

mentioning

confidence: 99%

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Noh

Chowdhury

Cho

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

The development of an anti-influenza vaccine with the potential for cross-protection against seasonal drift variants as well as occasionally emerging reassortant viruses is essential. In this study, we successfully generated a novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2) and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-γ-glutamic acid (γ-PGA)–based vaccine adjuvant systems that can act as a mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the incorporation of hydrophobic immunostimulatory 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination adjuvant γ-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA-PMQ immunization was able to prevent disease symptoms, confering complete protection against lethal infection with divergent influenza subtypes (H5N1, H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a mucosal adjuvant could be used for effective mucosal vaccines.

show abstract

“…HA2 gp is a relatively conserved protein, and some HA2 epitopes are even shared among HA subtypes (Kostolanský et al, 2002;Varečková et al, 2008). HA2-specific antibodies recognizing HA stem were shown to be protective (Gocník et al, 2007(Gocník et al, , 2008Prabhu et al, 2009;Sui et al, 2009;Wang et al, 2010;Staneková et al, 2011;Janulíková et al, 2012), though they do not mediate virus neutralization by blocking the receptor-binding site on HA. We therefore suggest that anti-stem HA antibodies could help individuals exposed to dangerous avian IAV to overcome the infection in a subclinical manner.…”

Section: Discussionmentioning

confidence: 99%

Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses

Janulíková¹,

Stropkovská²,

Bobišová³

et al. 2015

View full text Add to dashboard Cite

Summary. -In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.Keywords: avian influenza A viruses; sequential influenza A infection; antibody response; virus-neutralizing antibodies; HA2-specific antibodies; original antigenic sin * Corresponding author. E-mail: viruevar@savba.sk; phone: +421-2-59302427. Abbreviations: HA = hemagglutinin; IAV = influenza A virus; MAb = monoclonal antibody; OAS = original antigenic sin; VN = virus-neutralizing

show abstract

Monoclonal Antibodies against the Fusion Peptide of Hemagglutinin Protect Mice from Lethal Influenza A Virus H5N1 Infection

Cited by 109 publications

References 37 publications

Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses

Contact Info

Product

Resources

About