Mucosal IgA responses in influenza virus infections; thoughts for vaccine design

Riet, Elly van; Ainai, Akira; Suzuki, Tadaki; Hasegawa, Hideki

doi:10.1016/j.vaccine.2012.04.109

Cited by 123 publications

(94 citation statements)

References 97 publications

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“…While both vaccines elicited humoral responses in the ferrets, only LAIV provided protection from respiratory challenge with a live heterologous influenza virus. Potential mechanisms of sIgA protection may include blocking of viral host cell attachment at the site of initial mucosal infection, intracellular uptake of sIgA with blocking of viral uncoating, or redirection for uptake of influenza virus particles by respiratory macrophages or other phagocytes that can mediate intracellular killing and inhibition of influenza virus replication (27). These protective mechanisms afforded by LAIV may explain the beneficial effects of LAIV vaccination in adults despite the absence of serum HAI responses.…”

Section: Discussionmentioning

confidence: 99%

Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Hoft

Lottenbach

Blazevic

et al. 2017

Clin Vaccine Immunol

114

105

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Both live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV) induce protective immunity against influenza. There is evidence that LAIV induces superior protection in children, whereas IIV may induce superior protection in adults. The immune mechanisms responsible for these differences have not been identified. We previously compared LAIV and IIV in young children of 6 to 36 months of age, and we demonstrated that while both induced similar hemagglutination inhibition (HAI) antibody responses, only LAIV induced significant increases in T cell responses. In the present study, 37 healthy adult subjects of 18 to 49 years of age were randomized to receive seasonal influenza vaccination with LAIV or IIV. Influenza virus-specific HAI, T cell, and secretory IgA (sIgA) responses were studied pre- and postvaccination. In contrast to the responses seen in young children, LAIV induced only minimal increases in serum HAI responses in adults, which were significantly lower than the responses induced by IIV. Both LAIV and IIV similarly induced only transient T cell responses to replication-competent whole virus in adults. In contrast, influenza virus-specific sIgA responses were induced more strongly by LAIV than by IIV. Our previous studies suggest that LAIV may be more protective than IIV in young children not previously exposed to influenza virus or influenza vaccines due to increased vaccine-induced T cell and/or sIgA responses. Our current work suggests that in adults with extensive and partially cross-reactive preexisting influenza immunity, LAIV boosting of sIgA responses to hemagglutinin (HA) and non-HA antigenic targets expressed by circulating influenza virus strains may be an important additional mechanism of vaccine-induced immunity.

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Section: Discussionmentioning

confidence: 99%

Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Hoft

Lottenbach

Blazevic

et al. 2017

Clin Vaccine Immunol

114

105

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“…Parenteral vaccination induces serum IgG but not S-IgA, so vaccine efficacy is limited. In contrast, intranasal administration of an inactivated influenza vaccine elicits both S-IgA and IgG responses, thus improving the protective efficacy of current vaccination procedures (4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus

Suzuki

Kawaguchi

Ainai

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

119

103

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Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract.

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“…Immunization against influenza encompasses different kinds of immunity such as homologous protection (from strains included in the annually newly composed flu vaccines, e.g., H1N1) and cross-protection, with the later including homosubtypic protection against changing viruses (e.g., H1N2) and heterosubtypic protection (against different types of the virus, such as H3N2, or H5N1). 16 Mucosal IgA is also more cross-reactive and provides some protection against drift-and shift virus variants. 1 In particular, nasal live attenuated influenza vaccine (LAIV) is efficious even against strains not included, providing heterologous immunity, possibly mediated by mucosal IgA or cytotoxic T lymphocytes.…”

Section: Cross-protectionmentioning

confidence: 99%

Mucosal immunization in perspective

Rose

2014

Human Vaccines & Immunotherapeutics

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Mucosal IgA responses in influenza virus infections; thoughts for vaccine design

Cited by 123 publications

References 97 publications

Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus

Mucosal immunization in perspective

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