Chimeric Hemagglutinin-Based Influenza Virus Vaccines Induce Protective Stalk-Specific Humoral Immunity and Cellular Responses in Mice
| Autor: | Badiaa Bouzya, Klaus-Daniel Cortés Franco, Marie Van der Wielen, Ronan N. Rouxel, Roland Mainil, Florian Krammer, Arvind Rajabhathor, Bruce L. Innis, Peter Palese, Michael Schotsaert, Corey P. Mallett, Raffael Nachbagauer, Daniel Stadlbauer, Angela Choi, Adolfo García-Sastre |
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| Rok vydání: | 2019 |
| Předmět: |
Immunology
Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Biology Cross Reactions Antibodies Viral Virus Article Mice Immune system Orthomyxoviridae Infections Immunology and Allergy Live attenuated influenza vaccine Animals Humans AS03 Immunity Cellular General Medicine Virology Immunity Humoral Vaccination Disease Models Animal Immunization Influenza A virus Influenza Vaccines Humoral immunity biology.protein |
| Zdroj: | ImmunoHorizons. 3(4) |
| ISSN: | 2573-7732 |
| Popis: | The high variation of the influenza virus hemagglutinin (HA), particularly of its immunodominant head epitopes, makes it necessary to reformulate seasonal influenza virus vaccines every year. Novel influenza virus vaccines that redirect the immune response toward conserved epitopes of the HA stalk domain should afford broad and durable protection. Sequential immunization with chimeric HAs (cHAs) that express the same conserved HA stalk and distinct exotic HA heads has been shown to elicit high levels of broadly cross-reactive Abs. In the current mouse immunization studies, we tested this strategy using inactivated split virion cHA influenza virus vaccines (IIV) without adjuvant or adjuvanted with AS01 or AS03 to measure the impact of adjuvant on the Ab response. The vaccines elicited high levels of cross-reactive Abs that showed activity in an Ab-dependent, cell-mediated cytotoxicity reporter assay and were protective in a mouse viral challenge model after serum transfer. In addition, T cell responses to adjuvanted IIV were compared with responses to a cHA-expressing live attenuated influenza virus vaccine (LAIV). A strong but transient induction of Ag-specific T cells was observed in the spleens of mice vaccinated with LAIV. Interestingly, IIV also induced T cells, which were successfully recalled upon viral challenge. Groups that received AS01-adjuvanted IIV or LAIV 4 wk before the challenge showed the lowest level of viral replication (i.e., the highest level of protection). These studies provide evidence that broadly cross-reactive Abs elicited by cHA vaccination demonstrate Fc-mediated activity. In addition, cHA vaccination induced Ag-specific cellular responses that can contribute to protection upon infection. |
| Databáze: | OpenAIRE |
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