tetano
Editor, Senior Moderator
J Virol
. 2025 Jan 31:e0168524.
doi: 10.1128/jvi.01685-24. Online ahead of print. mRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity
Philip Samaan[SUP] 1 [/SUP], Chapin S Korosec[SUP] 2 3 [/SUP], Patrick Budylowski[SUP] 4 5 [/SUP], Serena L L Chau[SUP] 5 [/SUP], Adrian Pasculescu[SUP] 6 [/SUP], Freda Qi[SUP] 6 [/SUP], Melanie Delgado-Brand[SUP] 6 [/SUP], Tulunay R Tursun[SUP] 6 [/SUP], Geneviève Mailhot[SUP] 6 [/SUP], Roya Monica Dayam[SUP] 6 [/SUP], Corey R Arnold[SUP] 7 [/SUP], Marc-André Langlois[SUP] 7 [/SUP], Justin Mendoza[SUP] 5 [/SUP], Thomas Morningstar[SUP] 5 [/SUP], Ryan Law[SUP] 5 [/SUP], Erik Mihelic[SUP] 5 [/SUP], Salma Sheikh-Mohamed[SUP] 8 [/SUP], Eric Yixiao Cao[SUP] 8 [/SUP], Nimitha Paul[SUP] 9 [/SUP], Anjali Patel[SUP] 9 [/SUP], Keelia Quinn de Launay[SUP] 9 [/SUP], Jamie M Boyd[SUP] 9 [/SUP], Alyson Takaoka[SUP] 9 [/SUP], Karen Colwill[SUP] 6 [/SUP], Vitaliy Matveev[SUP] 5 [/SUP], Feng Yun Yue[SUP] 5 [/SUP], Allison McGeer[SUP] 1 6 [/SUP], Sharon Straus[SUP] 9 [/SUP], Anne-Claude Gingras[SUP] 6 10 [/SUP], Jane M Heffernen[SUP] 2 3 [/SUP], Mario Ostrowski[SUP] 1 4 5 8 9 11 [/SUP]
Affiliations
The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) and interleukin-2 (IL-2) T-cell responses and neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity on cellular and humoral responses to vaccination were additionally assessed. Mathematical modeling of the kinetics of spike-specific IFN-γ and IL-2 T-cell responses over 6 months post-second dose was bifurcated into recipients who exhibited gradual increases with doubling times of 155 and 167 days or decreases with half-lives of 165 and 132 days, respectively. Differences in kinetics did not correlate with clinical phenotypes. Serological anti-spike IgG, anti-receptor binding domain (RBD) IgG, anti-spike IgA, and anti-RBD IgA antibody levels otherwise decayed in all participants with half-lives of 63, 57, 79, and 46 days, respectively, alongside waning neutralizing capacity (t[SUB]1/2[/SUB] = 408 days). Spike-specific T-cell responses induced at 2-6 weeks positively correlated with live viral neutralization at 6 months post-second dose, especially in hybrid immune individuals. Participants with pre-existing cross-reactive T-cell immunity to SARS-CoV-2 exhibited greater spike-specific T-cell responses, reduced anti-RBD IgA antibody levels, and a trending increase in neutralization at 2-6 weeks post-second dose. Non-spike-specific T-cells predominantly targeted SARS-CoV-2 non-structural protein at 6 months post-second dose in cross-reactive participants. mRNA vaccination was lastly shown to induce off-target T-cell responses against unrelated antigens. In summary, vaccine-induced spike-specific T-cell immunity appeared to influence serological neutralizing capacity, with only a modest effect induced by pre-existing cross-reactivity.
Importance: Our findings provide valuable insights into the potential contributions of mRNA vaccine-induced spike-specific T-cell responses to the durability of neutralizing antibody levels in both uninfected and hybrid immune recipients. Our study additionally sheds light on the precise impacts of pre-existing cross-reactive T-cell immunity to severe acute respiratory syndrome coronavirus 2 on the magnitude and kinetics of cellular and humoral responses to vaccination. Accordingly, our data will help optimize the development of next-generation T cell-based coronavirus vaccines and vaccine regimens to maximize efficacy and durability.
Keywords: SARS-CoV-2; T-cell immunity; cross-reactivity; humoral immunity; hybrid immunity; mRNA vaccines.
. 2025 Jan 31:e0168524.
doi: 10.1128/jvi.01685-24. Online ahead of print. mRNA vaccine-induced SARS-CoV-2 spike-specific IFN-γ and IL-2 T-cell responses are predictive of serological neutralization and are transiently enhanced by pre-existing cross-reactive immunity
Philip Samaan[SUP] 1 [/SUP], Chapin S Korosec[SUP] 2 3 [/SUP], Patrick Budylowski[SUP] 4 5 [/SUP], Serena L L Chau[SUP] 5 [/SUP], Adrian Pasculescu[SUP] 6 [/SUP], Freda Qi[SUP] 6 [/SUP], Melanie Delgado-Brand[SUP] 6 [/SUP], Tulunay R Tursun[SUP] 6 [/SUP], Geneviève Mailhot[SUP] 6 [/SUP], Roya Monica Dayam[SUP] 6 [/SUP], Corey R Arnold[SUP] 7 [/SUP], Marc-André Langlois[SUP] 7 [/SUP], Justin Mendoza[SUP] 5 [/SUP], Thomas Morningstar[SUP] 5 [/SUP], Ryan Law[SUP] 5 [/SUP], Erik Mihelic[SUP] 5 [/SUP], Salma Sheikh-Mohamed[SUP] 8 [/SUP], Eric Yixiao Cao[SUP] 8 [/SUP], Nimitha Paul[SUP] 9 [/SUP], Anjali Patel[SUP] 9 [/SUP], Keelia Quinn de Launay[SUP] 9 [/SUP], Jamie M Boyd[SUP] 9 [/SUP], Alyson Takaoka[SUP] 9 [/SUP], Karen Colwill[SUP] 6 [/SUP], Vitaliy Matveev[SUP] 5 [/SUP], Feng Yun Yue[SUP] 5 [/SUP], Allison McGeer[SUP] 1 6 [/SUP], Sharon Straus[SUP] 9 [/SUP], Anne-Claude Gingras[SUP] 6 10 [/SUP], Jane M Heffernen[SUP] 2 3 [/SUP], Mario Ostrowski[SUP] 1 4 5 8 9 11 [/SUP]
Affiliations
- PMID: 39887249
- DOI: 10.1128/jvi.01685-24
The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) and interleukin-2 (IL-2) T-cell responses and neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity on cellular and humoral responses to vaccination were additionally assessed. Mathematical modeling of the kinetics of spike-specific IFN-γ and IL-2 T-cell responses over 6 months post-second dose was bifurcated into recipients who exhibited gradual increases with doubling times of 155 and 167 days or decreases with half-lives of 165 and 132 days, respectively. Differences in kinetics did not correlate with clinical phenotypes. Serological anti-spike IgG, anti-receptor binding domain (RBD) IgG, anti-spike IgA, and anti-RBD IgA antibody levels otherwise decayed in all participants with half-lives of 63, 57, 79, and 46 days, respectively, alongside waning neutralizing capacity (t[SUB]1/2[/SUB] = 408 days). Spike-specific T-cell responses induced at 2-6 weeks positively correlated with live viral neutralization at 6 months post-second dose, especially in hybrid immune individuals. Participants with pre-existing cross-reactive T-cell immunity to SARS-CoV-2 exhibited greater spike-specific T-cell responses, reduced anti-RBD IgA antibody levels, and a trending increase in neutralization at 2-6 weeks post-second dose. Non-spike-specific T-cells predominantly targeted SARS-CoV-2 non-structural protein at 6 months post-second dose in cross-reactive participants. mRNA vaccination was lastly shown to induce off-target T-cell responses against unrelated antigens. In summary, vaccine-induced spike-specific T-cell immunity appeared to influence serological neutralizing capacity, with only a modest effect induced by pre-existing cross-reactivity.
Importance: Our findings provide valuable insights into the potential contributions of mRNA vaccine-induced spike-specific T-cell responses to the durability of neutralizing antibody levels in both uninfected and hybrid immune recipients. Our study additionally sheds light on the precise impacts of pre-existing cross-reactive T-cell immunity to severe acute respiratory syndrome coronavirus 2 on the magnitude and kinetics of cellular and humoral responses to vaccination. Accordingly, our data will help optimize the development of next-generation T cell-based coronavirus vaccines and vaccine regimens to maximize efficacy and durability.
Keywords: SARS-CoV-2; T-cell immunity; cross-reactivity; humoral immunity; hybrid immunity; mRNA vaccines.