Non-neutralizing Antibodies Directed at Conservative Influenza Antigens

Седова, Е. С.; Scherbinin, D N; Лысенко, А. А.; Alekseeva, S. V.; Артемова, Э. А.; Шмаров, М. М.

doi:10.32607/20758251-2019-11-4-22-32

Cited by 37 publications

(35 citation statements)

References 61 publications

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“…It is also possible that non-neutralizing antibodies against the influenza virus conserved antigens, NP, M1 and M2, which may exert a protective function through ADCC, antibody-dependent phagocytosis or antibody-mediated complement-dependent cytotoxicity [ 49 ]. Additionally, T-cell mediated immune responses targeting the highly conserved NP have been associated with cross-reactive cytotoxic T lymphocytes [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

et al. 2021

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Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne infection is still unknown. Using the ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We demonstrate that a 48 hour exposure is sufficient for efficient transmission of H1N1 and H3N2 viruses. To test pre-existing immunity, a gap of 8–12 weeks between primary and secondary infections was imposed to reduce innate responses and ensure robust infection of donor animals with heterosubtypic viruses. We found that pre-existing H3N2 immunity did not significantly block transmission of the 2009 H1N1pandemic (H1N1pdm09) virus to immune animals. Surprisingly, airborne transmission of seasonal H3N2 influenza strains was abrogated in recipient animals with H1N1pdm09 pre-existing immunity. This protection from natural infection with H3N2 virus was independent of neutralizing antibodies. Pre-existing immunity with influenza B virus did not block H3N2 virus transmission, indicating that the protection was likely driven by the adaptive immune response. We demonstrate that pre-existing immunity can impact susceptibility to heterologous influenza virus strains, and implicate a novel correlate of protection that can limit the spread of respiratory pathogens through the air.

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Section: Discussionmentioning

confidence: 99%

Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

et al. 2021

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“…Antibodies induced by vaccines can be neutralizing or non-neutralizing. Non-neutralizing antibodies can contribute to anti-viral activities with mechanisms including antibody-medicated complementdependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) [reviewed (73)]. The yearly influenza vaccine induces both neutralizing and non-neutralizing antibodies that provide projection against the strains in the vaccine and closely related strains.…”

Section: Vaccine Risks For Antibody-dependent Enhancement (Ade)mentioning

confidence: 99%

Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

Ricke

2021

Front. Immunol.

120

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COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.

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“…Additionally, M2e-specific antibodies generally show non-neutralizing activity and their protections mainly depend on antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which assist in viral clearance [42][43][44]55]. Therefore, high level of M2e-specific IgG2a antibodies, which are more potent than other IgG subclasses in directing ADCC, is desirable for M2e-based vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Since the M2e induced immune protection mainly depends on antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), of which the efficiencies are different between IgG subtypes [42][43][44], we determined the titers of 3M2e-specific IgG1 and IgG2a. The Soc-3M2e soluble proteins mainly elicited IgG1, whereas mice immunized with T4-3M2e or a mixture of Soc-3M2e and phage T4 produced similar level of 3M2e-specific IgG1 and IgG2a antibodies (Fig.…”

Section: T4-3m2e Nanoparticles Induced Robust M2e-specific Antibodiesmentioning

confidence: 99%

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

Guo

Chen

et al. 2021

Preprint

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Developing influenza vaccines that protect against a broad range of viruses is a public health priority, and several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is immunogenic, and vaccine platforms that can incorporate multiple antigens with enhanced immunogenicity are desperately needed. In this study, we provided proof-of-concept for the development of next-generation influenza vaccine using T4 phage virus-like particle (VLP) platform. With extracellular domain of influenza matrix protein 2 (M2e) as a readout, we showed that more than 1,280 M2e molecules can be assembled on a 120×90 nanometer phage capsid to form T4-M2e VLPs, which are highly immunogenic and induced complete protection against influenza virus challenge without any addition adjuvant. Potentially, additional conserved antigens or molecular adjuvants could be incorporated into the T4-M2e VLPs to customize influenza vaccines to address different issues. All the components of T4 VLP vaccines can be mass-produced in E. coli in a short time, therefore, providing a rapid approach to deal with the potential influenza pandemic.

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Non-neutralizing Antibodies Directed at Conservative Influenza Antigens

Cited by 37 publications

References 61 publications

Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

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