ABSTRACT
BackgroundThe global COVID-19 pandemic has peaked but some countries such as China are reporting serious infectious outbreaks due to SARS-CoV-2 variants. Waning vaccine-derived immunogenicity and mutations in variants allowing vaccine evasion require new booster immunization approaches. We compared homologous and heterologous boosting in adults previously fully primed with a whole-virus inactivated COVID-19 vaccine. MethodsAt multiple sites in the Philippines we enrolled 430 adults (18-72 years) immunized with two doses of CoronaVac at least 3 months previously and randomly assigned them to receive homologous (CoronaVac, n = 216) or heterologous (recombinant protein vaccine, SCB-2019, n = 214) booster doses. Non-inferiority/superiority of the neutralizing antibody (NAb) response 15 days after boosting was measured by microneutralization against prototype SARS-CoV-2, and Delta and Omicron variants in subsets (50 per arm). Participants recorded solicited local and systemic adverse events for 7 days, unsolicited AEs until Day 29, and serious adverse events until Day 60. ResultsNAb geometric mean titers (GMT) against prototype on Day 15 were 744 (95% CI: 669-828) and 164 (143-189) in heterologous and homologous groups, respectively, with a heterologous/homologous GMT ratio of 4.63 (3.95-5.41), meeting both pre-defined non-inferiority and superiority criteria. Similarly, geometric mean-fold rises for NAb against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants were superior after heterologous SCB-2019 (range 3.01-4.66) than homologous CoronaVac (range 0.85-1.6) in an exploratory analysis. Reactogenicity and safety measures were evenly balanced between groups; the most frequent local reaction was mild or moderate injection site pain; mild or moderate headache and fatigue were the most frequent systemic adverse events. No vaccine-related serious adverse events were reported. ConclusionHeterologous boosting of CoronaVac-immunized adults with SCB-2019 was well tolerated with superior immunogenicity than homologous boosting, particularly for newly emerged variants, supporting use of SCB-2019 for booster vaccination.
ABSTRACT
BackgroundOngoing 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. MethodsWe assessed immunogenicity and reactogenicity of booster doses of different formulations of alum-adjuvanted SCB-2019 vaccine (9 g SCB-2019 with or without CpG-1018 adjuvant, or 30 g 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. ResultsAll SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 g SCB-2019+CpG+alum 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. ConclusionsBoosting 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 g SCB-2019+CpG+alum formulation.
ABSTRACT
BackgroundAs part of the accelerated development of prophylactic vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) we report a first-in-human dose-finding and adjuvant justification study of SCB-2019, a novel protein subunit vaccine candidate composed of a stabilised trimeric form of the spike (S)-protein produced in CHO-cells, combined with two different adjuvants. MethodsThis phase 1 study was done in one centre in Western Australia in 151 healthy adult volunteers in two age groups (18-54 and 55-75 years), allocated to 15 groups (nine young and six older adults) to receive two doses, 21 days apart, of placebo, or 3 g, 9 g or 30 g SCB-2019, alone or adjuvanted with AS03 or CpG/Alum. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding and ACE2-competitive binding IgG antibodies by ELISA, and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay; cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. FindingsWe report on 148 participants with at least 4 weeks follow-up post dose 2. Three participants withdrew, two for personal reasons and one with an unrelated SAE (pituitary adenoma). Vaccination was well tolerated, with few Grade 3 solicited adverse events (AE). Most local AEs were mild injection site pain, which were more frequent with formulations containing AS03 than CpG/Alum or unadjuvanted SCB-2019. Systemic AEs, mostly transient headache, fatigue or myalgia, were more frequent in young adults than older adults after the first dose, but similar after second doses. Unadjuvanted SCB-2019 elicited minimal immune responses, but SCB-2019 with fixed doses of AS03 or CpG/Alum induced high titres and seroconversion rates of binding and neutralising antibodies in both young and older adults. Titres were higher than those observed in a panel of COVID-19 convalescent sera in all AS03 groups and high dose CpG/Alum groups. Both adjuvanted formulations elicited Th1-biased CD4+ T cell responses. InterpretationSCB-2019 trimeric protein formulated with AS03 or CpG/Alum adjuvants elicited robust humoral and cellular immune responses against SARS-CoV-2 with high viral neutralising activity. Both adjuvanted formulations were well tolerated and are suitable for further clinical development. Clinical trial registrationClinicalTrials.gov identifier NCT04405908.
