CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques

Abstract

Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against SARS-CoV-2 infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for virologic control. However, direct data demonstrating a role of CD8 + T cells in vaccine protection has not yet been reported. In this study, we show that vaccine-elicited CD8 + T cells contribute substantially to virologic control following SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector-based vaccine Ad26.COV2.S or sham and then challenged them with 5x10 5 TCID 50 SARS-CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but showed rapid virologic control in nasal swabs and bronchoalveolar lavage by day 4 following challenge. However, administration of an anti-CD8α or anti-CD8β depleting monoclonal antibody in vaccinated animals prior to SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8 + T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.

Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors

“…Multiple studies showed a key role for SARS‐CoV‐2‐specific CD8 + cytotoxic T cells in the modulation and resolution of COVID‐19 pathogenesis. 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 Robust SARS‐CoV‐2‐specific CD8 + T cell immunity is associated with a mild disease outcome. 3 , 11 CD8 + T cells impair viral replication through recognition of viral peptide human leukocyte antigen class I (pHLA‐I) complexes displayed on the cell surface of infected cells, by which they accomplish rapid viral clearance and thereby reduce disease severity.…”

“…Multiple studies showed a key role for SARS‐CoV‐2‐specific CD8 + cytotoxic T cells in the modulation and resolution of COVID‐19 pathogenesis 3–10 . Robust SARS‐CoV‐2‐specific CD8 + T cell immunity is associated with a mild disease outcome 3,11 .…”

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

“…In conclusion, COVIRS represents a significant resource for understanding the early innate and adaptive immune responses to mRNA and adenovirus vectored COVID-19 vaccines, and how these responses relate to immunogenicity and reactogenicity. The generation of high titers of Spike-specific binding and neutralizing antibodies is currently the best correlate of protection following vaccination against SARS-CoV-2, although the contribution of vaccine-induced T cells in protection from SARS-CoV-2 infection is becoming increasingly apparent (McMahan et al, 2021, Liu et al, 2022). Identifying the factors that promote the optimal generation of vaccine-specific T and B cell responses is a key priority and our study provides a wealth of data to inform future rational vaccine design.…”

Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines

“…Animal models have demonstrated that CD8+ T cells offer protection against SARS-CoV-2 [32,33] even in the absence of detectable antibody [34]. Likewise, in a study of people with haematological malignancy and COVID-19, those with higher CD8+ T cells had a greater survival despite a blunted humoral immune response [35].…”