Murine Cross-Reactive Nonneutralizing Polyclonal IgG1 Antibodies Induced by Influenza Vaccine Inhibit the Cross-Protective Effect of IgG2 against Heterologous Virus in Mice.
Adjuvants, Immunologic
/ administration & dosage
Animals
Antibodies, Viral
/ biosynthesis
Binding, Competitive
Cross Protection
Immunoglobulin G
/ biosynthesis
Influenza A Virus, H1N1 Subtype
/ genetics
Influenza Vaccines
/ administration & dosage
Male
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides
/ administration & dosage
Orthomyxoviridae Infections
/ immunology
Protein Binding
Protein Isoforms
/ biosynthesis
Survival Analysis
Vaccination
/ adverse effects
CpG oligodeoxynucleotides
adjuvant
competition
cross-protection
influenza virus
vaccine
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
25
02
2020
accepted:
29
03
2020
pubmed:
10
4
2020
medline:
20
11
2020
entrez:
10
4
2020
Statut:
epublish
Résumé
Annual vaccination against influenza viruses is the most reliable and efficient way to prevent and control annual epidemics and protect from severe influenza disease. However, current split influenza vaccines are generally not effective against antigenically mismatched (heterologous) strains. To broaden the protective spectrum of influenza vaccines, adjuvants that can induce cross-reactive antibodies with cross-protection via Fc-mediated effector functions are urgently sought. Although IgG2 antibodies are generally more efficient than IgG1 antibodies in Fc-mediated effector functions, it is not yet clear which IgG isotypes show superior cross-protection against heterologous strains. It also remains unclear whether these IgG isotypes interfere with each other's protective effects. Here, we found that influenza split vaccine adjuvanted with aluminum salts, which predominantly induce cross-reactive IgG1, did not confer cross-protection against heterologous virus challenge in mice. In contrast, split vaccine adjuvanted with CpG oligodeoxynucleotides, which predominantly induce cross-reactive IgG2, showed cross-protection through the interaction of cross-reactive nonneutralizing IgG2 and alveolar macrophages, indicating the importance of cross-reactive nonneutralizing IgG2 for cross-protection. Furthermore, by using serum samples from immunized mice and isolated polyclonal antibodies, we show that vaccine-induced cross-reactive nonneutralizing IgG1 suppress the cross-protective effects of IgG2 by competitively inhibiting the binding of IgG2 to virus. Thus, we demonstrate the new concept that cross-reactive IgG1 may interfere with the potential for cross-protection of influenza vaccine. We propose that adjuvants that selectively induce virus-specific IgG2 in mice, such as CpG oligodeoxynucleotides, are optimal for heterologous protection.
Identifiants
pubmed: 32269125
pii: JVI.00323-20
doi: 10.1128/JVI.00323-20
pmc: PMC7307094
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Antibodies, Viral
0
CPG-oligonucleotide
0
Immunoglobulin G
0
Influenza Vaccines
0
Oligodeoxyribonucleotides
0
Protein Isoforms
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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