Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study

Abstract

Background Ongoing outbreaks of COVID-19 are driven by waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants which escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. Methods We assessed immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide-adjuvanted SCB-2019 vaccine (9 μg SCB-2019 with or without CpG-1018 adjuvant, or 30 μg SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. Results All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 μg SCB-2019 + CpG + aluminium hydroxide titers against wild-type S-protein were significantly higher than after ChAdOx1-S on Days 15 and 29, as were titers of neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. Conclusions Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 μg SCB-2019 + CpG + aluminium hydroxide formulation.

Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults

“…A previously reported study investigated heterologous boosting with SCB-2019 in Brazilian adults primed at least 6 months previously with the ChAdOx1-S COVID-19 vaccine with immunogenicity assays performed in the same laboratory as the present study [ 10 ]. Heterologous SCB-2019 was more immunogenic than homologous ChAdOx1-S; 15 days after boosting with SCB-2019 or ChAdOx1-S the respective neutralizing antibody GMTs were 822 versus 274 IU/mL against prototype SARS-CoV-2, 419 versus 123 (1/dilution) against Delta, and 65 versus 31 (1/dilution) against Omicron (B.1.1.529).…”

Heterologous boosting of neutralizing activity against Delta and Omicron SARS-CoV-2 variants in CoronaVac-primed adults; a randomized study with SCB-2019 vaccine

“…A previously reported study investigated heterologous boosting with SCB-2019 in Brazilian adults primed at least 6 months previously with the ChAdOx1-S vector COVID-19 vaccine with immunogenicity assays performed in the same laboratory as the present study [10]. These efficacy estimates were obtained against a background of circulating SARS-CoV-2 variants, mainly Delta, Gamma and Mu, but the high immunogenicity we show against the Omicron variants in this study support the notion that heterologous boosting with SCB-2019 would be efficacious against those new variants too.…”

“…Heterologous boosting has been extensively investigated with some of the many possible combinations of other COVID-19 vaccines including priming with mRNA vaccines and heterologous boosting with vector-based or whole inactivated (CoronaVac) vaccines and have generally resulted in higher immunogenicity [9][10][11][12][13]. Importantly, the higher responses with heterologous boosters includes improvements in neutralizing activity against the most recent circulating variants, the Omicron sub-lineages.…”

“…Sera prepared immediately from both blood draws were stored at -80°C for shipping to VisMederi srl (Siena, Italy) for the immunogenicity analyses. Immunogenicity was measured in all available sera from Days 1 and 15 as virus neutralizing antibodies (NAb) in a microneutralization assay using prototype Wuhan-Hu-1 SARS-CoV-2 [10]. Neutralizing responses were also measured in a subset of each vaccine group (n = 50 per subset) against the SARS-CoV-2 variants, Delta (B.1.617.2) and Omicron sub-lineages BA.1, BA.2, BA.4, and BA.5.…”

“…Decreases in vaccine-induced immunity due to the natural waning of antibody titers from the first month post-vaccination [5] and this lower susceptibility of the new variants to vaccine-induced immunity has led to the observation of lower protective efficacy from the first licensed COVID-19 vaccines [6,7]. This has driven the implementation of booster vaccination campaigns, especially with vaccines heterologous to the primary series in an effort to broaden the immune response and consequently the protection against new variants [8][9][10][11][12][13].…”