Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes

Autor: Hiroko Miyamoto, Kosuke Okuya, Akina Mori-Kajihara, Ayato Takada, Reiko Yoshida, Masahiro Kajihara, Rashid Manzoor, Takeshi Saito, Tadaki Suzuki, Masahiro Sato, Yurie Kida, Osamu Ichii, Hideaki Higashi, Michihito Sasaki, Shinji Saito, Tatsunari Kondoh
Rok vydání: 2020
Předmět:
Cross Protection
Hemagglutinin Glycoproteins
Influenza Virus
budding
Antibodies
Viral
medicine.disease_cause
Influenza A Virus
H2N2 Subtype
Madin Darby Canine Kidney Cells
law.invention
Mice
Influenza A Virus
H1N1 Subtype
law
antibody
Influenza A virus
Virus Release
Mice
Inbred BALB C
0303 health sciences
Antibodies
Monoclonal
broadly cross-reactive
Recombinant DNA
Female
Antibody
IgA
medicine.drug_class
Immunology
cross-protective immunity
Hemagglutinin (influenza)
Cross Reactions
Biology
Monoclonal antibody
Microbiology
Virus
03 medical and health sciences
Dogs
Orthomyxoviridae Infections
Neutralization Tests
Immunity
Virology
Influenza
Human
Vaccines and Antiviral Agents
medicine
Animals
Humans
hemagglutinin
Immunity
Mucosal
030304 developmental biology
Influenza A Virus
H5N1 Subtype
030306 microbiology
Antibodies
Neutralizing
nonneutralizing
Influenza A virus subtype H5N1
Immunoglobulin A
HEK293 Cells
Immunoglobulin G
Insect Science
biology.protein
Zdroj: J Virol
ISSN: 1098-5514
0022-538X
Popis: IgA antibodies on mucosal surfaces are known to play an important role in protection from influenza A virus (IAV) infection and are believed to be more potent than IgG for cross-protective immunity against IAVs of multiple hemagglutinin (HA) subtypes. However, in general, neutralizing antibodies specific to HA are principally HA subtype specific. Here, we focus on nonneutralizing but broadly cross-reactive HA-specific IgA antibodies. Recombinant IgG, monomeric IgA (mIgA), and polymeric secretory IgA (pSIgA) antibodies were generated based on the sequence of a mouse anti-HA monoclonal antibody (MAb) 5A5 that had no neutralizing activity but showed broad binding capacity to multiple HA subtypes. While confirming that there was no neutralizing activity of the recombinant MAbs against IAV strains A/Puerto Rico/8/1934 (H1N1), A/Adachi/2/1957 (H2N2), A/Hong Kong/483/1997 (H5N1), A/shearwater/South Australia/1/1972 (H6N5), A/duck/England/1/1956 (H11N6), and A/duck/Alberta/60/1976 (H12N5), we found that pSIgA, but not mIgA and IgG, significantly reduced budding and release of most of the viruses from infected cells. Electron microscopy demonstrated that pSIgA deposited newly produced virus particles on the surfaces of infected cells, most likely due to tethering of virus particles. Furthermore, we found that pSIgA showed significantly higher activity to reduce plaque sizes of the viruses than IgG and mIgA. These results suggest that nonneutralizing pSIgA reactive to multiple HA subtypes may play a role in intersubtype cross-protective immunity against IAVs. IMPORTANCE Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities in vitro. These recombinant antibodies did not show "classical" neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with lAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from lAVs of multiple HA subtypes, including viruses with pandemic potential.
Databáze: OpenAIRE
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