Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine

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.

Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized, Open-Label Trial

“…Repeated vaccination may boost antibodies to conserved epitopes and those present in egg-adapted vaccines rather than eliciting neutralizing antibodies against vaccine viruses or circulating influenza viruses [ 7 ]. Vaccine platforms that do not rely on egg-based production, including standard-dose cell culture–based inactivated influenza vaccine and recombinant-hemagglutinin (HA) protein vaccine with higher HA antigen content, may induce broader and higher immune responses to circulating influenza strains of viruses than egg-based vaccines [ 8 , 9 ]. Immune responses to annual revaccination may also differ by preexisting antibody levels, antigenic similarity between vaccine viruses in consecutive seasons, and antigen content [ 10 , 11 ].…”

Ex vivo assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors

“…Golgi-Plug containing Brefeldin A (BD Biosciences, San Diego, CA) was added 3 h into the culture (1 μg/mL) as previously described. 73 After the incubation, cells were stained with surface markers for 30 min at 4°C followed by fixation with 4% paraformaldehyde (Sigma-Aldrich, St. Louis, MO) at 4°C for 10 min. Intracellular staining was performed at room temperature for 30 min after cells were permeabilized with saponin.…”

An optimized flow cytometry protocol for simultaneous detection of T cell activation induced markers and intracellular cytokines: Application to SARS-CoV-2 immune individuals

“…Among the TCR stimulation dependent markers, CD137 appears to be particularly interesting given its kinetics of expression after antigen recognition and its biologic role to provide a survival signal to activated T cells, both CD4+ and CD8+ T lymphocytes ( Watts, 2005 ) ( Wen et al, 2002 ). In parallel, emerging evidence are pointing to the value of assessing the cytokine profile of AIM+ T cells to better describe the intensity and features of ongoing immune response ( Painter, 2021 ; Yu et al, 2021 ; Braun et al, 2020 ).…”