Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People

Abstract

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4+- and CD8+-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older (n = 54) compared with the COVID-19-naive younger adults (n = 121). Notably, older participants’ neutralizing antibodies were 10 times lower than the younger’s antibody titers (p < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ+ and IFNγ+IL-2+TNFα+ cells among specific CD4+ T cells, and the frequency of specific CD8+ T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults (p < 0.0001 and p = 0.0018, respectively). However, COVID-19-recovered older participants (n = 51) had greater antibody and T-cell responses, including IFNγ+ and IFNγ+IL-2+TNFα+-specific CD4+ T cells (p < 0.0001), as well as TNFα+-specific CD8+ T cells (p < 0.001), than COVID-19-naive older adults. We also observed that “inflammageing” and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4+ and CD8+ T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people.

Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial

“…Increasing studies have demonstrated a higher immune response to mRNA COVID-19 vaccines in individuals previously infected with SARS-CoV-2 compared to antigen-naïve subjects [ 32 , 33 , 34 ]. The results obtained in this study support the observed evidence and add new information to the few data published regarding the elderly population [ 35 , 36 ]. Although this heightened immune response seems to be related to repeated exposure, the underlying mechanisms remain unclear [ 37 ].…”

Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years

“…Data at baseline and three-month post-vaccination have been previously described. 3 The booster dose was administered to NH residents between September and November 2021, as soon as recommended by the French Health Authorities and from at least six months after the initial vaccination. Data before and after the booster vaccine are reported in the present study.…”

“… 1 Previous reports demonstrated a low postvaccination antibody and cellular response against SARS-CoV-2 in older people compared to younger. 2 , 3 We notably reported that the antibody response and the functional T-Cell response to SARS-CoV-2 were impaired three months after initial SARS-CoV-2 BNT162b2 mRNA vaccination series (two doses) in NH residents, including the neutralizing response against the B.1.1.7 (Alpha) variant which was dominant in the first months of 2021. 3 This data suggested that a third dose should be considered to improve protective immunity in this at-risk population.…”

“… 2 , 3 We notably reported that the antibody response and the functional T-Cell response to SARS-CoV-2 were impaired three months after initial SARS-CoV-2 BNT162b2 mRNA vaccination series (two doses) in NH residents, including the neutralizing response against the B.1.1.7 (Alpha) variant which was dominant in the first months of 2021. 3 This data suggested that a third dose should be considered to improve protective immunity in this at-risk population. Since the summer of 2021, numerous national health authorities have recommended such a booster vaccination in older people and other immunocompromised subjects, but the Delta variant was already dominant at this time, and the efficiency of such vaccinal schemes against the current dominant variants of concern (VoC) B.1.617.2 (Delta) and B.1.1.529 (Omicron) needs to be assessed.…”

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

“…The effect of age on SARS-CoV-2 vaccine responses has been studied [7-9, 29-33], but the sex differential impact of age has not been reported previously. Furthermore, studies investigating frailty have not found an effect on antibody responses [34-36], but have reported that frailty increases the risk of post-vaccination breakthrough infection [37, 38], suggesting that the immunogenicity studies may have been under-powered to observe an effect of frailty or that lack of consideration of biological sex obscured the effect.…”