Long-term effects of homologous and heterologous SARS-CoV-2 vaccination
on humoral and cellular immune responses
Abstract
Background: Humoral and cellular immune responses to SARS-CoV-2
vaccines wane with time. In the COV‑ADAPT cohort, we recently studied
both immunological components and their interdependencies following
different vaccine combinations before (T1) and up to three months after
second immunization (T2). This follow-up investigated the stability of
long-term immune responses and aimed to identify predictive markers.
Methods: We assessed humoral (anti-spike-RBD-IgG,
neutralization capacity, avidity) and cellular (spike-induced T-cell
interferon‑γ release) immune responses three-seven months after
secondary vaccination (T3) in blood samples of 318 healthcare workers
with previous homologous ChAdOx1 nCoV-19 (ChAdOx1), homologous BNT162b2
or heterologous ChAdOx1/BNT162b2 vaccinations. Results: At T3,
homologous ChAdOx1 vaccination resulted in significantly lower
anti-spike-RBD-IgG (152±151 BAU/ml) as compared to heterologous
ChAdOx1/BNT162b2 (388±300 BAU/ml) and homologous BNT162b2 (435±327
BAU/ml). In all groups, anti-spike-RBD-IgG (T3) exceeded antibody levels
before second vaccination (T1). T-cell interferon-γ release following
heterologous ChAdOx1/BNT162b2 vaccination was significantly higher at T3
(1062±2083 mIU/ml) vs. T1 (680±1691 mIU/ml), yet did not differ
significantly between the three groups at T3. Associations between
humoral and cellular responses were found at T3 (all groups combined).
Additionally, the early cellular response (at T1) was significantly
associated with late (T3) humoral (ChAdOx1/BNT162b2, BNT162b2/BNT162b2)
and cellular responses (all groups). In contrast to T2, neutralization
capacity at T3 was significantly higher for ChAdOx1/BNT162b2 and
BNT162b2/BNT162b2 vs. ChAdOx1/ChAdOx1. Conclusions: We
identified (i) long-term interdependencies between the humoral and the
cellular immune system, (ii) observed distinct waning dynamics following
different vaccination regimes, and (iii) uncovered early T-cell
responses as a useful predictor of long-term immune responses.