Roles of antibodies to influenza A virus hemagglutinin, neuraminidase, and M2e in conferring cross protection

Kim, Yujin; Ko, Eunju; Kim, Min‐Chul; Lee, Yuna; Kim, Ki-Hye; Jung, Yu‐Jin; Kang, Sang-Moo

doi:10.1016/j.bbrc.2017.09.011

Cited by 17 publications

(13 citation statements)

References 21 publications

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“…Previous studies have shown that Fc-FcγR interactions contribute little to the protection of mice treated with anti-A(H1N1)pdm09 polyclonal serum against homologous challenge (19). Initially, we sought to confirm this phenotype in the context of a protective polyclonal anti-NA immune serum.…”

Section: Resultsmentioning

confidence: 99%

“…Whether this contributes to protection in vivo is unknown. Kim et al (19) have shown that FcγR knockout (KO) mice lose slightly more weight than wild-type (WT) counterparts when infected with A(H1N1)pdm09 preincubated with polyclonal sera raised to recombinant N1 NA. Finally, Kawaoka and colleagues recently demonstrated that human A(H1N1)pdm09 anti-NA antibodies that target the lateral side of the NA head not only protect in an Fc-dependent manner but may also drive antigenic drift in the lateral portion of the NA head (20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

Job

Ysenbaert

Smet

et al. 2019

mBio

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There is a pressing need for next-generation influenza vaccine strategies that are better able to manage antigenic drift and the cocirculation of multiple drift variants and that consistently improve vaccine effectiveness. Influenza virus NA is a key target antigen as a component of a next-generation vaccine in the influenza field, with evidence for a role in protective immunity in humans. However, mechanisms of protection provided by antibodies directed to NA remain largely unexplored. Herein, we show that antibody Fc interaction with Fcγ receptors (FcγRs) expressed on effector cells contributes to viral control in a murine model of influenza. Importantly, a chimeric mouse-human IgG1 with no direct antiviral activity was demonstrated to solely rely on FcγRs to protect mice from disease. Therefore, antibodies without NA enzymatic inhibitory activity may also play a role in controlling influenza viruses and should be of consideration when designing NA-based vaccines and assessing immunogenicity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

Job

Ysenbaert

Smet

et al. 2019

mBio

View full text Add to dashboard Cite

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“…Although a truly stratifying correlation between in vitro activity and in vivo activity was not resolved, 1086F8 and 1092D4, which exhibited the greatest in vivo activity against B/Brisbane/60/2008 virus, including suppressing the virus to below detectable levels in several mice, were the most potent hMAbs in inhibiting B/Brisbane/60/2008 virus replication in vitro (IC 50 , <0.5 μg/ml) but were not superior to the other hMAbs in their ELLA activity. Several animal studies demonstrated previously that Fc-mediated effector functions such as ADCC substantially contribute to the in vivo antiviral activity of NA-specific antibodies (27–30). Our study did not attempt to define the relative scontribution of Fc-mediated antibody functions; however, our resulting panel of NA-specific hMAbs is likely to serve future utility in defining mechanisms of action of NA Ab-mediated protection.…”

Section: Discussionmentioning

confidence: 99%

Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells

Piepenbrink

Nogales

Basu

et al. 2019

mBio

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Although most seasonal inactivated influenza vaccines (IIV) contain neuraminidase (NA), the extent and mechanisms of action of protective human NA-specific humoral responses induced by vaccination are poorly resolved. Due to the propensity of influenza virus for antigenic drift and shift and its tendency to elicit predominantly strain-specific antibodies, humanity remains susceptible to waves of new strains of seasonal viruses and is at risk from viruses with pandemic potential for which limited or no immunity may exist. Here we demonstrate that the use of IIV results in increased levels of influenza B virus (IBV) NA-specific serum antibodies. Detailed analysis of the IBV NA B cell response indicates concurrent expansion of IBV NA-specific peripheral blood plasmablasts 7 days after IIV immunization which express monoclonal antibodies with broad and potent antiviral activity against both IBV Victoria and Yamagata lineages and prophylactic and therapeutic activity in mice. These IBV NA-specific B cell clonal lineages persisted in CD138+ long-lived bone marrow plasma cells. These results represent the first demonstration that IIV-induced NA human antibodies can protect and treat influenza virus infection in vivo and suggest that IIV can induce a subset of IBV NA-specific B cells with broad protective potential, a feature that warrants further study for universal influenza vaccine development. IMPORTANCE Influenza virus infections continue to cause substantial morbidity and mortality despite the availability of seasonal vaccines. The extensive genetic variability in seasonal and potentially pandemic influenza strains necessitates new vaccine strategies that can induce universal protection by focusing the immune response on generating protective antibodies against conserved targets such as regions within the influenza neuraminidase protein. We have demonstrated that seasonal immunization stimulates neuraminidase-specific antibodies in humans that are broad and potent in their protection from influenza B virus when tested in mice. These antibodies further persist in the bone marrow, where they are expressed by long-lived antibody-producing cells, referred to here as plasma cells. The significance in our research is the demonstration that seasonal influenza immunization can induce a subset of neuraminidase-specific B cells with broad protective potential, a process that if further studied and enhanced could aid in the development of a universal influenza vaccine.

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“…It was found that immune sera against NA and M2e were superior in terms of improving heterosubtypic protection and survival than anti-HA Abs induced by the split seasonal vaccine. Interestingly, the co-administration of NA and M2e5XVLP immune sera gave rise to a synergistic heterologous protection effect (107).…”

Section: Antibodies Against Iav External Proteinsmentioning

confidence: 99%

Protective Antibodies Against Influenza Proteins

Padilla-Quirarte

López-Guerrero

Gutiérrez‐Xicoténcatl

et al. 2019

Front. Immunol.

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The influenza A virus infection continues to be a threat to the human population. The seasonal variation of the virus and the likelihood of periodical pandemics caused by completely new virus strains make it difficult to produce vaccines that efficiently protect against this infection. Antibodies (Abs) are very important in preventing the infection and in blocking virus propagation once the infection has taken place. However, the precise protection mechanism provided by these Abs still needs to be established. Furthermore, most research has focused on Abs directed to the globular head domain of hemagglutinin (HA). However, other domains of HA (like the stem) and other proteins are also able to elicit protective Ab responses. In this article, we review the current knowledge about the role of both neutralizing and non-neutralizing anti-influenza proteins Abs that play a protective role during infection or vaccination.

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Roles of antibodies to influenza A virus hemagglutinin, neuraminidase, and M2e in conferring cross protection

Cited by 17 publications

References 21 publications

Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

Fcγ Receptors Contribute to the Antiviral Properties of Influenza Virus Neuraminidase-Specific Antibodies

Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells

Protective Antibodies Against Influenza Proteins

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