ABSTRACT
The coronavirus pandemic is a severe infectious respiratory disease which caused massive loss worldwide. Thailand was affected by the wild-type, and the Delta variant started in mid-2021. Due to the shortage of effective vaccines, the ministry of public health of Thailand suggested the heterologous vaccine scheme, which comprises inactivated COVID-19 vaccine (CoronaVac) and an adenoviral-based vectored vaccine (ChAdOx1). However, data on the humoral and cellular immune responses of the single or 2 shots of inactivated vaccine followed by the adenoviral-based vaccine are very limited. In this current study, the sera from participants who received either single or 2 shots of CoronaVac followed by the ChAdOx1 vaccine were evaluated for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG. The cytokine level was also assessed using Luminex immunoassay. The PBMC were collected to evaluate spike-specific T-cell and B-cell responses. Participants who received 2 shots of CoronaVac followed by ChAdOx1 possessed significantly (P<0.0001) higher levels of spike RBD-specific IgG. They also exhibited a higher level of CD4+T-cell and IFN-gamma than those who received only 1 shot of CoronaVac followed by the ChAdOx1 vaccine. The volunteers who received two shots of CoronaVac followed by ChAdOx1 had a significantly (p<0.01) higher marginal B-cell response against wild-type SARS-CoV-2 S peptides than those who received only one shot of CoronaVac followed by ChAdOx1. Surprisingly, the class switch B-cell response to Delta variant SARS-CoV-2 S peptides of the volunteers who received 1 shot of CoronaVac followed by ChAdOx1 was significantly (p<0.01) higher than those who received 2 shots of CoronaVac. However, participants who received only a single shot of inactivated vaccine followed by an adenoviral-based vectored vaccine possessed a higher level of TNF-alpha and IL-6. This study indicated that boosting the ChAdOx1 as a third dose after completing 2 shots of CoronaVac induced strong humoral and cellular immune responses.
ABSTRACT
BackgroundResponding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. MethodImmunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. ResultBetween April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks (873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152, and I/I group 108.2, 95% CI 77-152; all p<0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p<0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. ConclusionThe I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.
