ABSTRACT
Background: Primary SARS-CoV-2 vaccination has been shown to wane with time and provide lower protection from disease with new viral variants, prompting the WHO to recommend the administration of booster doses. We determined the safety and immunogenicity of homologous or heterologous boosters with ChAdOx1 nCoV-19 (COVISHIELD™) or BBV152 (COVAXIN®), the two vaccines used widely for primary immunization in India, in participants who had already received two primary doses of these vaccines. Methods: Participants primed with two doses each of COVISHIELD™ or COVAXIN® 12-36 weeks previously, were randomised to receive either COVISHIELD™ or COVAXIN® booster in a 1:1 ratio. The primary outcome was day 28 post-booster anti-spike IgG seropositivity and secondary outcomes were anti-spike IgG levels and assessment of safety and reactogenicity. The results of 90 days intention-to-treat analysis are presented. This trial is registered with ISRCTN (CTRI/2021/08/035648). Findings: In the COVISHIELD™ primed group with 200 participants, the seropositivity 28 days post booster in the heterologous COVAXIN® arm was 99% and non-inferior to the homologous COVISHIELD™ arm, which was also 99% (difference 0%; 95% CI: -2.8% to 2.7%). The geometric mean concentration (GMC) of anti-spike antibodies following heterologous COVAXIN® boost on day 28 was 36,190.78 AU/mL (95% CI: 30,526.64-42,905.88) while the GMC following homologous COVISHIELD™ boost was 97,445.09 AU/mL (82,626.97-114,920.7). In the COVAXIN® primed group with 204 participants, the seropositivity 28 days post booster in the heterologous COVISHIELD™ arm was 100% and non inferior to the homologous COVAXIN® arm which was 96% (difference 4%, 95% CI: 0.2%-7.8%). The GMC following heterologous COVISHIELD™ boost was 241,681.6 AU/mL (95% CI: 201,380.2-290,048.3) compared to homologous COVAXIN® boost, which was 48,473.94 AU/mL (95% CI: 38,529.56-60,984.95). The day 28 geometric mean ratio (GMR) of the anti-spike IgG between the heterologous and homologous boosted arms was 0.42 (95% CI: 0.34-0.52) in the COVISHIELD™ primed group and 5.11 (95% CI: 3.83-6.81) in the COVAXIN® primed group. There were no related serious adverse events reported in any group. Interpretation: Homologous and heterologous boosting with COVISHIELD™ or COVAXIN® in COVISHIELD™ or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD™ after COVAXIN® prime offers the best immune response among the four combinations evaluated. Funding: Azim Premji Foundation and Bill and Melinda Gates Foundation.
ABSTRACT
SARS-CoV-2 Omicron subvariants such as BA.2.12.1, BA.4 and BA.5 have been spreading rapidly and become dominant worldwide. Here we report the homologous or heterologous booster effects of S-268019-b, a recombinant spike protein vaccine with the squalene-based adjuvant A-910823 in cynomolgus macaques. In macaques which had been primed with S-268019-b or mRNA vaccines, boosting with S-268019-b enhanced neutralizing antibodies (NAb) against ancestral SARS-CoV-2. Since boosting with the antigen without adjuvant did not efficiently restore NAb titers, adjuvant A-910823 was essential for the booster effect. Importantly, boosting with S-268019-b enhanced NAb against all of the Omicron subvariants we tested, including BA.2.12.1, BA.4 and BA.5, in comparison to two vaccine doses. Additionally, expansion of Omicron-specific B cells was confirmed after boosting with S-268019-b. These results indicate that a booster dose of S-268019-b with the adjuvant enhances the neutralization breadth.
Subject(s)
COVID-19 , Squalene , Animals , SARS-CoV-2 , COVID-19/prevention & control , Vaccines, Synthetic/genetics , Adjuvants, Immunologic , Macaca fascicularis , Antibodies, Neutralizing , VaccinationABSTRACT
As vaccine resources were distributed unevenly worldwide, sometimes there might have been shortages or delays in vaccine supply; therefore, considering the use of heterogeneous booster doses for Coronavirus disease 2019 (COVID-19) might be an alternative strategy. Therefore, we aimed to review the data available to evaluate and compare the effectiveness and safety of heterologous booster doses with homologous booster doses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We searched relevant studies up to 27 April 2022. Random-effects inverse variance models were used to evaluate the vaccine effectiveness (VE) and its 95% confidence interval (CI) of COVID-19 outcomes and odds ratio (OR) and its CI of safety events. The Newcastle-Ottawa quality assessment scale and Cochrane Collaboration's tool were used to assess the quality of the included cohort studies. A total of 23 studies involving 1,726,506 inoculation cases of homologous booster dose and 5,343,580 inoculation cases of heterologous booster dose was included. The VE of heterologous booster for the prevention of SARS-CoV-2 infection (VEheterologous = 96.10%, VEhomologous = 84.00%), symptomatic COVID-19 (VEheterologous = 56.80%, VEhomologous = 17.30%), and COVID-19-related hospital admissions (VEheterologous = 97.40%, VEhomologous = 93.20%) was higher than homologous booster. Compared with homologous booster group, there was a higher risk of fever (OR = 1.930, 95% CI, 1.199-3.107), myalgia (OR = 1.825, 95% CI, 1.079-3.089), and malaise or fatigue (OR = 1.745, 95% CI, 1.047-2.906) within 7 days after boosting, and a higher risk of malaise or fatigue (OR = 4.140, 95% CI, 1.729-9.916) within 28 days after boosting in heterologous booster group. Compared with homologous booster group, geometric mean neutralizing titers (GMTs) of neutralizing antibody for different SARS-CoV-2 variants and response rate of antibody and gama interferon were higher in heterologous booster group. Our findings suggested that both homologous and heterologous COVID-19 booster doses had great effectiveness, immunogenicity, and acceptable safety, and a heterologous booster dose was more effective, which would help make appropriate public health decisions and reduce public hesitancy in vaccination.
Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Fatigue , Humans , Immunization, Secondary , SARS-CoV-2ABSTRACT
Given emerging evidence of immune escape in the SARS-CoV-2 Omicron viral variant, and its dominance, effectiveness of heterologous and homologous boosting schedules commonly used in low-to-middle income countries needs to be re-evaluated. We conducted a test-negative design using consolidated national administrative data in Malaysia to compare the effectiveness of homologous and heterologous BNT162b2, CoronaVac, and AZD1222 booster vaccination against SARS-CoV-2 infection in predominant-Delta and predominant-Omicron periods. Across both periods, homologous CoronaVac and AZD1222 boosting demonstrated lower effectiveness than heterologous boosting for CoronaVac and AZD1222 primary vaccination recipients and homologous BNT162b2 boosting. Broadly, marginal effectiveness was smaller by 40-50 percentage points in the Omicron period than the Delta period. Without effective and accessible second-generation vaccines, heterologous boosting using BNT162b2 for inactivated and vectored primary vaccination recipients is preferred.