1. Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques
- Author
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Masanori Shiohara, Saori Suzuki, Shintaro Shichinohe, Hirohito Ishigaki, Misako Nakayama, Naoki Nomura, Masashi Shingai, Toshiki Sekiya, Marumi Ohno, Sayaka Iida, Naoko Kawai, Mamiko Kawahara, Junya Yamagishi, Kimihito Ito, Ryotarou Mitsumata, Tomio Ikeda, Kenji Motokawa, Tomoyoshi Sobue, Hiroshi Kida, Kazumasa Ogasawara, and Yasushi Itoh
- Subjects
viruses ,Antibodies, Viral ,Influenza A Virus, H1N1 Subtype ,Orthomyxoviridae Infections ,Influenza, Human ,Animals ,Humans ,B-Lymphocytes ,General Veterinary ,General Immunology and Microbiology ,Genes, Immunoglobulin ,Vaccination ,Public Health, Environmental and Occupational Health ,Virion ,virus diseases ,Antibodies, Neutralizing ,Somatic hypermutation ,Influenza ,Macaca fascicularis ,Infectious Diseases ,Vaccines, Inactivated ,Influenza Vaccines ,Nonhuman primate model ,Immunoglobulin repertoire ,Molecular Medicine ,Vaccine - Abstract
The All-Japan Influenza Vaccine Study Group has been developing a more effective vaccine than the current split vaccines for seasonal influenza virus infection. In the present study, the efficacy of formalin- and/or β-propiolactone-inactivated whole virus particle vaccines for seasonal influenza was compared to that of the current ether-treated split vaccines in a nonhuman primate model. The monovalent whole virus particle vaccines or split vaccines of influenza A virus (H1N1) and influenza B virus (Victoria lineage) were injected subcutaneously into naïve cynomolgus macaques twice. The whole virus particle vaccines induced higher titers of neutralizing antibodies against H1N1 influenza A virus and influenza B virus in the plasma of macaques than did the split vaccines. At challenge with H1N1 influenza A virus or influenza B virus, the virus titers in nasal swabs and the increases in body temperatures were lower in the macaques immunized with the whole virus particle vaccine than in those immunized with the split vaccine. Repertoire analyses of immunoglobulin heavy chain genes demonstrated that the number of B-lymphocyte subclones was increased in macaques after the 1st vaccination with the whole virus particle vaccine, but not with the split vaccine, indicating that the whole virus particle vaccine induced the activation of vaccine antigen-specific B-lymphocytes more vigorously than did the split vaccine at priming. Thus, the present findings suggest that the superior antibody induction ability of the whole virus particle vaccine as compared to the split vaccine is attributable to its stimulatory properties on the subclonal differentiation of antigen-specific B-lymphocytes.
- Published
- 2022