Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory

Abstract

Longitudinal studies have revealed large interindividual differences in antibody responses induced by SARS-CoV-2 mRNA vaccines. Thus, we performed a comprehensive analysis of adaptive immune responses induced by three doses of the BNT162b2 SARS-CoV-2 mRNA vaccines. The responses of spike-specific CD4+ T cells, CD8+ T cells and serum IgG, and the serum neutralization capacities induced by the two vaccines declined 6 months later. The 3rd dose increased serum spike IgG and neutralizing capacities against the wild-type and Omicron spikes to higher levels than the 2nd dose, and this was supported by memory B cell responses, which gradually increased after the 2nd dose and were further enhanced by the 3rd dose. The 3rd dose moderately increased the frequencies of spike-specific CD4+ T cells, but the frequencies of spike-specific CD8+ T cells remained unchanged. T cells reactive against the Omicron spike were 1.3-fold fewer than those against the wild-type spike. The early responsiveness of spike-specific CD4+ T, circulating T follicular helper cells and circulating T peripheral helper cells correlated with memory B cell responses to the booster vaccination, and early spike-specific CD4+ T cell responses were also associated with spike-specific CD8+ T cell responses. These findings highlight the importance of evaluating cellular responses to optimize future vaccine strategies.

High-resolution kinetics and cellular determinants of antibody response to SARS-CoV-2 over two years after COVID-19 vaccination

“…Furthermore, the highest antibody responses and maintenance observed in response to infection underscore the importance of hybrid immunity, which needs to be taken into consideration by future vaccination strategies. These findings corroborate those of other studies showing increased humoral responses after the 3 rd booster dose 15,30,33,45 and when having hybrid immunity 6,23,45 . This increase in the magnitude and persistence of antibody responses after a booster by infection or vaccination may be attributed to immunization-induced cumulative affinity-enhancement of somatic hypermutations that differentiate into specific-memory B cells and long-lived bone marrow plasma cells 46 .…”

“…All participants had detectable antibody responses 25 months after the 1 st vaccine dose and 15 months after the booster (3 rd ) dose, which is in line with our previous study 12 . Our findings confirm the kinetic pattern of IgG and IgA surges following subsequent immunizations, which restore and increase humoral responses, previously observed 9,[30][31][32] . It also aligns with a few studies that have reported a non-constant decelerating waning of antibodies after COVID-19 vaccination and SARS-CoV-2 infection 8,33,34 , which results in a biphasic decline with an initial rapid decay during the first few months, followed by a phase of slower decline and stabilization.…”

IgG anti-RBD levels during 8-month follow-up post-vaccination with BNT162b2 and mRNA-1273 vaccines in healthcare workers: A one-center study

“…In addition, in individuals on dialysis (Kaiser et al, 2021;Yau et al, 2022) or in immunocompromised patients (Obeid et al, 2022), it has been observed that the mRNA-1273 vaccine induces a higher humoral response, which would support the use of this vaccine in vulnerable populations. In addition, we observed that older individuals vaccinated with BNT162b2 had lower antibody levels (< 70 years old), as has already been reported (Naaber et al, 2021;Bai et al, 2022;Herzberg et al, 2022). To the contrary, as far as we know, we described for the first time individuals vaccinated with mRNA-1273 who presented the opposite behaviour: older volunteers (< 70 years old) appeared to present with a higher humoral response than younger participants.…”

Prognostic Factors Associated with the Severe Course of a New Coronavirus Infection

“…У большинства пациентов с COVID-19 наблюдалось легкое течение заболевания. Однако, у части пациентов отмечалось быстрое ухудшение (особенно в течение 7-14 дней) с развитием острого респираторного дистресс-синдрома (ОРДС), что приводило к летальному исходу [3,4]. Оценка риска развития тяжелых форм инфекции, также понимание патогенетических механизмов заболевания являются, несомненно, актуальными проблемами здравоохранения [5].…”