ABSTRACT
Background: The occurrence of side effects, such as thrombotic events, related to vaccination with ChAdOx1 nCoV-19, led in many countries to heterologous messenger RNA (mRNA) boosting. Method(s): We tested the antibody response to SARS-CoV- 2 spike protein 4 and 15 weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/ BNT) comparing data of homologous regimen (BNT/BNT, ChAd/ ChAd), subjects positive for SARS-CoV- 2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19. We also evaluated again at 28 weeks after completion of the primary schedule any differences between residual antibody response resulting from a heterologous course and the one deriving from homologous regimen. Healthy subjects naive for SARS-CoV- 2 infection were assessed for serum IgG anti-S- RBD response 21 days after priming (T1), 4 (TFULL), 15 (T15W) and 28 (T28W) weeks after booster dose. Result(s): The median IgG anti-S- RBD levels at TFULLof Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S- RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescent were significantly lower than ChAd/ BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S- RBD titer > 75 AU/ml, correlated high neutralizing titer, was of 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescent. At T15Wthe titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S- RBD decline was reduced for ChAd/ChAd and similar for other combinations. At T28W weeks) there was a significant difference of median ChAd/BNT vs ChAd/ Chad (p = 0.0166), with 36.11 AU/ml and 5.5 AU/ml, respectively. The decay of antispike antibody to RBD at 170 days was 1342 AU/ week for ChAd/ChAd, and 19.22 AU/week for ChAD/BNT. Conclusion(s): Our data highlight the magnitude of IgG anti-S- RBD response in the ChAd/BNT dosing and higher IgG levels were still detectable after 28 weeks after booster dose supporting the current national guidelines for heterologous boosting. The analysis of effectiveness of vaccine combinations in this cohort is ongoing, during the omicron variant spread.