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J Virol. 2019 Jul 24. pii: JVI.00947-19. doi: 10.1128/JVI.00947-19. [Epub ahead of print]

Protein vaccination directs the CD4+ T cell response towards shared protective epitopes that can be recalled after influenza infection.

Author information

1
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
2
David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA andrea_sant@urmc.rochester.edu.

Abstract

Vaccination is widely used to generate protective immunity to influenza. CD4+ T cells contribute in diverse ways to protective immunity, most notably for provision of help for production of neutralizing antibodies. Several recent reports have suggested that influenza infection elicits CD4+ T cells whose specificity only partially overlaps with those elicited by vaccination. This finding has raised serious concerns regarding the utility of currently licensed inactivated influenza vaccines and novel protein-based vaccines. Here, using controlled animal models that allowed a broad sampling of the CD4+ T cell repertoire, we have evaluated protein vaccine- vs. infection-generated CD4+ T cell epitopes. Our studies revealed that all the infection-elicited CD4+ T cell epitope specificities are also elicited by protein vaccination, although immunodominance hierarchies can differ. Finally, using a reverse-engineered influenza virus, and a heterologous protein vaccination and infection challenge strategy, we show that protein vaccine-elicited CD4+ memory T cells are recalled and boosted after infection and provide early help to accelerate HA-specific antibody responses. The early CD4+ T cell response and HA-specific antibody production is associated with lowered viral titers during the infection challenge. Our data lend confidence in current protein-based vaccines ability to elicit influenza-specific CD4+ T cells that can potentiate protective immunity upon influenza virus infection.Importance. Most current and new influenza vaccine candidates consist of single or combinations of influenza virus proteins. For these vaccines to elicit CD4+ T cells that can be recalled after infection, the peptides epitopes should be shared between the two modes of confrontation. There have recently been questions raised regarding the relatedness of epitope selection by influenza infection and protein vaccination. However, the studies reported here show that protein-based vaccines overlap with those elicited by infection and that CD4+ T cells primed by protein vaccines are recalled and contribute to protection of the host from a future infection.

PMID:
31341045
DOI:
10.1128/JVI.00947-19

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