Emergence of Fatal Avian Influenza in New England Harbor Seals

Anthony, Simon J.; Leger, Judy St.; Pugliares, Katie R.; Ip, Hon S.; Chan, Joseph M.; Carpenter, Zachary; Navarrete-Macias, Isamara; Sanchez-Leon, M. D.; Saliki, Jerry T.; Pedersen, Janice C.; Karesh, William B.; Daszak, Peter; Rabadán, Raúl; Rowles, Teri; Lipkin, W. Ian

doi:10.1128/mbio.00166-12

Cited by 178 publications

(175 citation statements)

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“…The anti-N8 antibodies generated by our fusion also showed a very broad binding profile; over half of the isolated MAbs exhibited binding to both the North American and the Eurasian N8 lineages. Importantly, we found strong reactivity to potential pandemic viruses like H3N8, which caused a severe outbreak in harbor seals in New England in 2012, as well as against the N8 NA of the newly emerging, highly pathogenic H5N8 viruses (26,30,31,36,37). The H3N8 subtype is also important, since it was speculated to be the cause of a human pandemic in 1889 (38).…”

Section: Discussionmentioning

confidence: 95%

Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

Wohlbold

Chromikova

Tan

et al. 2016

J Virol

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Between November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10-and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibody in vivo using a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality. IMPORTANCEAvian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no specific therapeutics or vaccines are available against the H10N8 influenza virus subtype. We generated a panel of H10-and N8-reactive MAbs. Although these antibodies may practically be developed into therapeutic agents, characterizing the protective potential of MAbs that have targets other than the HA globular head domain will provide insight into novel antibody-mediated mechanisms of protection and help to better understand correlates of protection for influenza A virus infection. R ecently, avian influenza A viruses of the H10 subtype have been reported to infect seals and humans and have generated concern over their pandemic potential. Three human cases of H10N8 virus have been reported in China so far, two of which were fatal (1-3). Furthermore, an avian H10N7 strain was found to be the etiological agent responsible for the massive die-off harbor seals in the Baltic Sea, an epidemic that killed more than 10% of the local seal population (4-6). The receptor binding profile of H10 viruses is currently debated (7-12), but the subtype has been proven to cause ...

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Section: Discussionmentioning

confidence: 95%

Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

Wohlbold

Chromikova

Tan

et al. 2016

J Virol

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“…These antibodies were not only protective against a panel of H3N2 strains and an H3N8 virus but also provided robust protection against a heterosubtypic challenge with avian H7N1 and H10N7 isolates, demonstrating a breadth that spans both clades of the group 2 HA-expressing viruses. This breadth is important in light of growing concerns about the pandemic potential of H3N2 variant (H3N2v) viruses and H3N8 viruses isolated from New England harbor seals and other zoonotic H3 strains (12,34,38), as well as H4-, H7-, and H10-expressing viruses that infect humans occasionally (11,(39)(40)(41)(42)(43). Importantly, this vaccination strategy also induced high titers of stalk-reactive antibodies against the H7 HA from the emerging Chinese H7N9 virus (10).…”

Section: Discussionmentioning

confidence: 99%

Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses

Margine

Krammer

Hai

et al. 2013

J Virol

185

161

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f Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.

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“…In many cases where disease has caused significant mortality in wild marine mammals, it has been linked to viruses, including morbillivirus, phocine distemper and influenza virus [51][52][53][54][55] .…”

Section: Sampling Techniquesmentioning

confidence: 99%