Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS‐CoV‐2 vaccination

Abstract

Background Homologous and heterologous SARS‐CoV‐2 vaccinations yield different spike protein‐directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods COV‐ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV‐19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV‐19/BNT162b2. We assessed humoral (anti‐spike‐RBD‐IgG, neutralizing antibodies, and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses in blood samples up to 2 weeks before (T1) and 2–12 weeks following secondary immunization (T2). Results Initial vaccination with ChAdOx1 nCoV‐19 resulted in lower anti‐spike‐RBD‐IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV‐19 at T2 (anti‐spike‐RBD‐IgG: ChAdOx1 nCoV‐19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV‐19 413 ± 461 BAU/ml, both p < .001; spike‐induced T‐cell interferon‐γ release: ChAdOx1 nCoV‐19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV‐19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2‐boostered groups at T2. For ChAdOx1 nCoV‐19, no booster effect on T‐cell activation could be observed. We found associations between anti‐spike‐RBD‐IgG levels (ChAdOx1 nCoV‐19/BNT162b2 and homologous BNT162b2) and T‐cell responses (homologous ChAdOx1 nCoV‐19 and ChAdOx1 nCoV‐19/BNT162b2) from T1 to T2. Additionally, anti‐spike‐RBD‐IgG and T‐cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions Interdependencies between humoral and cellular immune responses differ between common SARS‐CoV‐2 vaccination regimes. T‐cell activation is unlikely to compensate for poor humoral responses.

Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination

“…Although neutralizing antibody titers were lower in subjects who had received 2 doses of mRNA vaccine than in patients, these antibodies displayed higher avidity. This observation is in line with previous reports of a significant increase in neutralization and avidity after the administration of a second vaccine dose [ 17 , 33 ]. However, this immune response was not retained in the case of the Omicron variant, for which both neutralizing titers and avidity were lower.…”

Immunogenicity evaluation after BNT162b2 booster vaccination in healthcare workers

“…Therefore, the COV-ADAPT study has presented the results obtained in HCW receiving various vaccination protocols. Homologous ChAdOx1 nCoV-19, homologous BNT162b2 or heterologous ChAdOx1nCoV-19/BNT162b2 vaccinations protocols have induced different Spike protein-directed humoral and cellular immune responses 46 . An Israeli study has shown that BNT162b2, homologous booster dose was associated with a lower rate infection rate 47 .…”

Long‐term effects of homologous and heterologous SARS‐CoV‐2 vaccination on humoral and cellular immune responses

“…10,11 In the COV-ADAPT cohort, we recently studied the humoral and cellular immune responses and their interdependencies following different vaccine combinations before (T1) and up to 3 months after the second immunization (T2). 12 This follow-up investigated the stability of long-term immune responses and aimed to identify predictive markers. Thus, we assessed humoral (anti-spike-RBD-IgG, neutralization capacity and avidity) and cellular (spike-induced T-cell interferonγ release) immune re- The last group was not analyzed separately due to the low n-number (for characterization of study participants see Table S1).…”

“… 10 , 11 In the COV‐ADAPT cohort, we recently studied the humoral and cellular immune responses and their interdependencies following different vaccine combinations before (T1) and up to 3 months after the second immunization (T2). 12 This follow‐up investigated the stability of long‐term immune responses and aimed to identify predictive markers. Thus, we assessed humoral (anti‐spike‐RBD‐IgG, neutralization capacity and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses 3–7 months after the second immunization (T3) in blood samples of 320 healthcare workers of the COV‐ADAPT cohort with previous homologous ChAdOx1 nCoV‐19 (ChAdOx1, n = 26), homologous BNT162b2 ( n = 49), heterologous ChAdOx1/BNT162b2 ( n = 243) or heterologous ChAdOx1 /mRNA‐1273 ( n = 2) vaccinations (Figure S1 ; all participants provided written informed consent).…”