IMMUNOGENICITY OF A HETEROLOGOUS INACTIVATED AND mRNA COVID-19 COMBINATION VACCINE REGIMEN

heterologous inactivated and mRNA COVID-19 vaccine regimen

Abstract

Vaccine shortages and side effects have caused many people to have received a mixed anti-corona virus vaccine regimen using two different types of vaccine (heterologous regimen). In this cross-sectional study, we aimed to evaluate the immunogenicity among healthcare professionals of the following vaccine regimens: a combination of the CoronaVac vaccine (CV) followed by the BNT162b2 vaccine (BNT) (CV/BNT) (n = 76) compared to the two-dose CV regimen (CV/CV) (n = 170) or a two-dose BNT vaccine regimen (BNT/BNT) (n = 19) in order to determine if the CV/BNT regimen may be considered as an alternative to the CV/CV or BNT/BNT regimens. Subjects received the CV/BNT regimen, at short-intervals (21-28 days apart) or long-intervals (≥7 weeks apart). We obtained the following from each subject: serum total immunoglobulin (Ig), immunoglobulin G (IgG) and A (IgA) levels against the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein (anti-RBD Ig, anti-RBD IgG and anti-S IgA (reported as a sample-to-calibrator (S/C) relative light unit ratio), respectively) 21-35 days after the second dose of their vaccine and calculated the geometric mean titer (GMT) (95%CI) for these levels. We evaluated the neutralization activity (NA) of each sample using an ELISA-based surrogate virus neutralization test (sVNT) against wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the following SARS-CoV-2 variants: B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and BA.4/5 (Omicron). A total of 265 subjects were included in the study, 65% female. The mean (±standard deviation) age of study subjects was 37 (±12) (range: 14-59) years. The GMT (95%CI) of the long and short interval total anti-RBD Ig levels elicited by the CV/BNT regimen against the wild-type SARS-CoV-2 variant were 1,042 (828-1,311) and 10,485 (7,228-15,209) U/ml, the anti-RBD IgG were 1,475 (1,267-1,716) and 2,683 (2,075-3,469) BAU/ml and the median (IQR) anti-S IgA S/C ratios were 6.6 (4.9-9.0) and 9 (7.8-9.0, respectively. The GMT (95%CI) of total anti-RBD Ig level elicited by the CV/CV regimen against the wild-type SARS-CoV-2 variant was 98 (83-116) U/ml, the anti-RBD IgG was 128 (114-144) BAU/ml and the median (IQR) anti-S IgA S/C ratio was 0.9 (0.6-1.8). The GMT (95%CI) of the total anti-RBD Ig level elicited by the BNT/BNT regimen against the wild-type SARS-CoV-2 variant was 1,963 (1,378-2,798) U/ml, the anti-RBD IgG was 1,651 (1,182-2,306) BAU/ml, and the median (IQR) anti-S IgA S/C ratio was 5.6 (4.5-8.4). The GMT of the total anti-RBD Ig levels elicited by the short- and long-interval CV/BNT regimens were significantly higher (<0.001, <0.001) than the CV/CV regimen, and significantly higher (0.019, <0.001) than the BNT/BNT regimen, respectively. The GMT of the anti-RBD IgG levels elicited by the short- and long-interval CV/BNT regimen were significantly higher (<0.001, <0.001) than the CV/CV regimen but not significantly different (0.814 and 0.774) than the BNT/BNT regimen, respectively. The median (IQR) NA elicited by the short-interval CV/BNT regimen against the wild-type, Alpha, Beta, Delta and Omicron variants were 96 (93-97), 85 (79-89), 77 (69-83), 93 (89-95), and 27 (22-35), respectively, the long-interval CV/BNT regimen were 97 (97-98), 98 (97-98), 95 (94-96), 97 (97-98), and 54 (38-84), respectively, the CV/CV regimen were 67 (49-79), 42 (29-58), 35(21-47), 49 (36-63), and 11 (9-15) and the BNT/BNT regimen were 97 (96-98), 94 (88-95), 89 (80-91), 97 (95-98) and 33 (27-42), respectively. The median NA levels against the Omicron variant elicited by the short- and long-interval CV/BNT regimen were significantly higher (<0.001, <0.001) than the CV/CV regimen but not significantly different (0.416, 0.492) than the BNT/BNT regimen. In summary, the CV/BNT regimen provided significantly higher anti-RBD IgG levels than the CV/CV regimen and similar levels than the BNT/BNT regimen. We conclude the CV/BNT regimen may be a reasonable alternative for initial vaccination. Further studies are needed to determine the long-term effects of these regimens.