Safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit COVID-19 vaccine in healthy 12-17 year-old adolescents (preprint)

We previously demonstrated efficacy of the COVID-19 vaccine candidate, SCB-2019, in adults in the SPECTRA phase 2/3 efficacy study. We extended the study to include 1278 healthy 12-17-year-old adolescents in Belgium, Colombia and the Philippines who received either two doses of SCB-2019 or placebo 21 days apart, to assess immunogenicity as neutralizing antibodies against prototype SARS-CoV-2 and variants of concern, and safety and reactogenicity as solicited and unsolicited adverse events with a comparator group of young adults (18-25 years). In participants with no evidence of prior SARS-CoV-2 infection SCB-2019 immunogenicity in adolescents was non-inferior to that in young adults; respective geometric mean neutralizing titers (GMT) against prototype SARS-CoV-2 14 days after the second vaccination were 271 IU/mL (95% CI: 211-348) and 144 IU/mL (116-178). Most adolescents (1077, 84.3%) had serologic evidence of prior SAR-CoV-2 exposure at baseline; in these seropositive adolescents neutralizing GMTs increased from 173 IU/mL (135-122) to 982 IU/mL (881-1094) after the second dose. Neutralizing titers against Delta and Omicron BA SARS-CoV-2 variants were also increased, most notably in those with prior exposure. SCB-2019 vaccine was well tolerated with generally mild or moderate, transient solicited and unsolicited adverse events that were comparable in adolescent vaccine and placebo groups except for injection site pain - reported after 20% of SCB-2019 and 7.3% of placebo injections. SCB-2019 vaccine was highly immunogenic against SARS-CoV-2 prototype and variants in adolescents, especially in those with evidence of prior exposure, with comparable immunogenicity to young adults.

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

Background: The 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. Methods: At 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. Results: NAb 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. Conclusion: Heterologous 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.

Immunogenicity of SCB-2019 COVID-19 Vaccine Compared to Four Approved Vaccines (preprint)

A significant correlation has been shown between the binding antibody responses against original SARS-CoV-2-S-protein all performed in one laboratory and vaccine efficacy of four approved COVID-19 vaccines. We therefore assessed the immune response against original SARS-CoV-2 elicited by the adjuvanted S-Trimer vaccine, SCB-2019 + CpG/alum, in the same assay and laboratory. When compared with four approved vaccines immune responses to SCB-2019 predicted 81% − 94% efficacy against the original strain and 75–94% against the Alpha variant (B.1.1.7). Immunogenicity comparisons to original strain and variants of concern (VOC) should be considered as a basis for authorization of vaccines because efficacy studies now have predominantly VOC cases.

A first-in-human evaluation of the safety and immunogenicity of SCB-2019, an adjuvanted, recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19 in healthy adults; a phase 1, randomised, double-blind, placebo-controlled trial (preprint)

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.