Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Abstract

The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have drawn strong attention to another arm of acquired immunity, CD8+ T cells, which are also called killer T cells. Recent evidence accumulated during the coronavirus disease 2019 (COVID-19) pandemic has revealed that even variants of SARS-CoV-2 that escaped from neutralizing-antibodies that were induced by either infection or vaccination could not escape from CD8+ T cell-mediated immunity. In addition, although traditional vaccine platforms, such as inactivated virus and subunit vaccines, are less efficient in inducing CD8+ T cells, newly introduced platforms for SARS-CoV-2, namely, mRNA and adenoviral vector vaccines, can induce strong CD8+ T cell-mediated immunity in addition to inducing neutralizing antibodies. However, CD8+ T cells function locally and need to be at the site of infection to control it. To fully utilize the protective performance of CD8+ T cells, it would be insufficient to induce only memory cells circulating in blood, using injectable vaccines; mucosal immunization could be required to set up CD8+ T cells for the optimal protection. CD8+ T cells might also contribute to the pathology of the infection, change their function with age and respond differently to booster vaccines in comparison with antibodies. Herein, we overview cutting-edge ideas on CD8+ T cell-mediated immunity that can enable the rational design of vaccines for respiratory viruses.

Dynamic immune landscape in vaccinated-BA.5-XBB.1.9.1 reinfections revealed a 5-month protection-duration against XBB infection and a shift in immune imprinting

“…3 B and D), which was consistent with previous findings that inactivated virus and subunit vaccines are less efficient in inducing CD8 + T cells. 3 , 25 However, post BA.5 infection, virus-specific CD8 + T cell responses peaked at D14 with a higher proportion of Tnaïve and TEMRA phenotypes, showing a slower kinetics compared to CD4 + T cell response ( Fig. 6 ).…”

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

“… 14 , 36 , 37 Recent evidence accumulated during the SARS-CoV-2 pandemic has revealed that variants that escaped from nAbs that were induced by either natural infection or vaccination could not escape from CD8 T cell-mediated immunity. 38 As the vaccine-elicited antibody response wore off, most CD4 and CD8 T cells responses were preserved. 39 Accordingly, T cells have been credited with playing a key role in the sustained vaccine-mediated protection against hospitalization and death.…”

mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection

“…Based on the role of antigen-specific T cells in protective immunity against SARS-CoV-2 infection, it is becoming increasingly clear that successful vaccines need to engage the cellular adaptive immune response. 70 , 71 , 72 Indeed, humoral immune responses may be less effective against SARS-CoV-2 variants. 73 , 74 Conversely, SARS-CoV-2-specific CD8 T cell responses, which target a broad range of epitopes, remain largely intact against variants.…”