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

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 ELISAbased 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-typeSARS- 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 antiRBD Ig level elicited by the BNT/BNT regimen against the wild-type SARSCoV- 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( 2147), 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.