Abstract
The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period, and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all four included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.
Highlights
IntroductionA total of three influenza proteins are incorporated in the viral membrane: the hemagglutinin (HA), neuraminidase (NA), and M2 proton channel, while the virion core contains the matrix (M1), nuclear export (NEP), non-structural (NS1) proteins, and eight viral ribonucleoproteins (vRNP)
The influenza virus is an enveloped virus with a relatively simple structure
A total of 10 healthy males and non-pregnant females aged 18 to 49 years old were enrolled at Vanderbilt University Medical Center (VUMC) during March to October 2019
Summary
A total of three influenza proteins are incorporated in the viral membrane: the hemagglutinin (HA), neuraminidase (NA), and M2 proton channel, while the virion core contains the matrix (M1), nuclear export (NEP), non-structural (NS1) proteins, and eight viral ribonucleoproteins (vRNP). Owing to the genomic instability, influenza viruses gain frequent antigenic alterations through antigen drift (point mutations in the viral genome) and antigen shift (gene segment exchange between viral genomes) [2]. This is the reason why a yearly vaccine is required. The combination of strains is standardized annually in compliance with World Health Organization (WHO) [3] and Committee for Medicinal Products for Human Use (CHMP) recommendations (EU) [4], or United States Public Health Service requirements (in the USA) [5], to provide protection against the strains expected to circulate in the upcoming influenza season
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