Induction of Cross-Reactive Antibodies to Novel H7N9 Influenza Virus by Recombinant Newcastle Disease Virus Expressing a North American Lineage H7 Subtype Hemagglutinin

Goff, Peter H.; Krammer, Florian; Hai, Rong; Seibert, Christopher W.; Margine, Irina; García‐Sastre, Adolfo; Palese, Peter

doi:10.1128/jvi.01085-13

Cited by 50 publications

(52 citation statements)

References 27 publications

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“…These results and recent reports from other groups show that there is substantial cross-reactivity between H7 strains in mice and humans (20,(36)(37)(38)(39) but to a much lesser extent in ferrets (24). This cross-reactivity is most likely induced by antibodies against antigenic site A, which is highly conserved in avian H7 isolates.…”

Section: Discussionsupporting

confidence: 65%

Divergent H7 Immunogens Offer Protection from H7N9 Virus Challenge

Krammer

Albrecht

Tan

et al. 2014

J Virol

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The emergence of avian H7N9 viruses in humans in China has renewed concerns about influenza pandemics emerging from Asia. Vaccines are still the best countermeasure against emerging influenza virus infections, but the process from the identification of vaccine seed strains to the distribution of the final product can take several months. In the case of the 2009 H1N1 pandemic, a vaccine was not available before the first pandemic wave hit and therefore came too late to reduce influenza morbidity. H7 vaccines based on divergent isolates of the Eurasian and North American lineages have been tested in clinical trials, and seed strains and reagents are already available and can potentially be used initially to curtail influenza-induced disease until a more appropriately matched H7N9 vaccine is ready. In a challenge experiment in the mouse model, we assessed the efficacy of both inactivated virus and recombinant hemagglutinin vaccines made from seed strains that are divergent from H7N9 from each of the two major H7 lineages. Furthermore, we analyzed the cross-reactive responses of sera from human subjects vaccinated with heterologous North American and Eurasian lineage H7 vaccines to H7N9. Vaccinations with inactivated virus and recombinant hemagglutinin protein preparations from both lineages raised hemagglutination-inhibiting antibodies against H7N9 viruses and protected mice from stringent viral challenges. Similar cross-reactivity was observed in sera of human subjects from a clinical trial with a divergent H7 vaccine. Existing H7 vaccine candidates based on divergent strains could be used as a first line of defense against an H7N9 pandemic. In addition, this also suggests that H7N9 vaccines that are currently under development might be stockpiled and used for divergent avian H7 strains that emerge in the future. IMPORTANCESporadic human infections with H7N9 viruses started being reported in China in the early spring of 2013. Despite a significant drop in the number of infections during the summer months of 2013, an increased number of cases has already been reported for the 2013-2014 winter season. The high case fatality rate, the ability to bind to receptors in the human upper respiratory tract in combination with several family clusters, and the emergence of neuraminidase inhibitor-resistant variants that show no loss of pathogenicity and the ability to transmit in animal models have raised concerns about a potential pandemic and have spurred efforts to produce vaccine candidates. Here we show that antigen preparations from divergent H7 strains are able to induce protective immunity against H7N9 infection.

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Section: Discussionsupporting

confidence: 65%

Divergent H7 Immunogens Offer Protection from H7N9 Virus Challenge

Krammer

Albrecht

Tan

et al. 2014

J Virol

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“…Here we chose to express the HA and NA proteins from two isolates of the novel Chinese H7N9 influenza virus, A/Anhui/1/13 and A/ Shanghai/1/13 20,21 . These are timely examples, but the described protocol can be used for expression of any influenza A and B HA or NA proteins and can be adapted to express any other secreted viral or cellular proteins.…”

Section: Introductionmentioning

confidence: 99%

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Margine

Palese

Krammer

2013

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The baculovirus expression system is a powerful tool for expression of recombinant proteins. Here we use it to produce correctly folded and glycosylated versions of the influenza A virus surface glycoproteins -the hemagglutinin (HA) and the neuraminidase (NA). As an example, we chose the HA and NA proteins expressed by the novel H7N9 virus that recently emerged in China. However the protocol can be easily adapted for HA and NA proteins expressed by any other influenza A and B virus strains. Recombinant HA (rHA) and NA (rNA) proteins are important reagents for immunological assays such as ELISPOT and ELISA, and are also in wide use for vaccine standardization, antibody discovery, isolation and characterization. Furthermore, recombinant NA molecules can be used to screen for small molecule inhibitors and are useful for characterization of the enzymatic function of the NA, as well as its sensitivity to antivirals. Recombinant HA proteins are also being tested as experimental vaccines in animal models, and a vaccine based on recombinant HA was recently licensed by the FDA for use in humans. The method we describe here to produce these molecules is straight forward and can facilitate research in influenza laboratories, since it allows for production of large amounts of proteins fast and at a low cost. Although here we focus on influenza virus surface glycoproteins, this method can also be used to produce other viral and cellular surface proteins. Video LinkThe video component of this article can be found at

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“…We recently showed that ferret antiserum against these H7 ca viruses had cross-reactivity to the H7N9 virus (30). The cross-reactivity between divergent H7 viruses was also reported for the inactivated virus, recombinant protein, or virus-like particle (VLP) vaccines studied in mice (31)(32)(33) or humans (34). Another Eurasian-lineage H7N3 LAIV reassortant with an alternative internal gene backbone was reported to induce cross-reactive antibodies to H7N9 (35), indicating that an H7 LAIV might be protective against a divergent H7 strain.…”

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confidence: 99%

Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

Chen

Baz

et al. 2014

J Virol

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IMPORTANCEIn response to the recent avian H7N9 influenza virus infection in humans, we developed a live attenuated H7N9 influenza vaccine (LAIV) with two amino acid substitutions in the viral HA protein that improved vaccine yield by 10-fold in chicken embryonated eggs, the substrate for vaccine manufacture. The two amino acids also improved the antigen yield for inactivated H7N9 vaccines, demonstrating that this finding could great facilitate the efficiency of H7N9 vaccine manufacture. The candidate H7N9 LAIV was immunogenic and protected ferrets against homologous and heterologous wild-type H7 virus challenge, making it suitable for use in protecting humans from H7 infection.

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Induction of Cross-Reactive Antibodies to Novel H7N9 Influenza Virus by Recombinant Newcastle Disease Virus Expressing a North American Lineage H7 Subtype Hemagglutinin

Cited by 50 publications

References 27 publications

Divergent H7 Immunogens Offer Protection from H7N9 Virus Challenge

Divergent H7 Immunogens Offer Protection from H7N9 Virus Challenge

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

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