Results of a randomized, placebo-controlled, observer-blinded, phase 1/2 trial support further development of COVID-19 vaccine candidate GBP510, a recombinant SARS-CoV-2 protein nanoparticle vaccine adjuvanted with AS03. These findings were published in The Lancet.
This phase 1/2 study was conducted at 14 sites in South Korea between February and May 2021 to evaluate the safety and immunogenicity of COVID-19 vaccine candidate GBP510. Eligible patients included adults who were unvaccinated and had no history of COVID-19 infection. In phase 1, patients (n=40) aged between 19 and 55 years were randomly assigned in a 2:1:1 ratio to receive two 10-mg doses of GBP510 adjuvanted with AS03 (group 1), two 10-mg doses of unadjuvanted GBP510 (group 2), or placebo. In phase 2, patients (n=240) aged between 19 and 85 years were randomly assigned in a 2:2:1:1 fashion to receive either a 10-mg dose of adjuvanted GBP510 (group 1), a 25-mg dose of adjuvanted GBP510 (group 3), a 25-mg dose of unadjuvanted GBP510 (group 4), or placebo. The safety and immunogenicity of the adjuvanted and unadjuvanted GP510 vaccines were evaluated via comparisons between all patient groups.
Among a total of 328 patients included at enrollment, the median age was 42 (range, 19-80) years, 45.1% were men, and the median BMI was 24.1 (range, 18.0-29.9) kg/m2.
Within 7 days of vaccination, the rate of solicited local adverse events (AEs) was lowest among patients in the placebo group (21.3%), followed by those in groups 2 (50.0%), 4 (66.7%), 1 (89.1%), and 3 (92.3%). For solicited systemic AEs, the lowest rates were observed among patients in the placebo group (57.4%), followed by those in groups 2 (70.0%), 4 (70.6%), 1 (85.2%), and 3 (85.6%). The majority of AEs were of mild to moderate severity.
The highest rate of Grade 3 AEs occurred among patients in group 3 (4.7%). No Grade 4 AEs were observed in any patient group.
Laboratory results were abnormal in 4 patients following receipt of the GBP510 vaccine, with changes in triglycerides noted in 3 patients and mild leukopenia in 1.
The geometric mean concentrations (GMC) of anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin (Ig)G antibodies ranged between 11.0 and 16.3 binding antibody units (BAU)/mL at baseline. At day 28 following receipt of the first vaccine dose, the GMC of anti-SARS-CoV-2 RBD IgG antibodies were 111.9 and 129.0 BAU/mL among patients in groups 1 and 3, respectively, and 37.7 and 28.6 BAU/mL among those in groups 2 and 4, respectively.
At day 42, the GMC of anti-SARS-CoV-2 RBD IgG antibodies was 2163.6 and 2599.2 BAU/mL among patients in groups 1 and 3, respectively, and 155.3 and 112.4 BAU/mL among those in groups 2 and 4, respectively. Owing to these results, immune responses at day 42 were significantly greater among patients who received the adjuvanted GBP510 vaccine compared with those who received the unadjuvanted vaccine (P <.0001).
Results were similar in regard to neutralizing antibody titers. At day 42, neutralizing antibody titers were more than 10-times higher among patients in groups 1 and 3 (geometric mean titers [GMTs], 1369.0 and 1431.5 IU/mL, respectively; P <.0001) compared with those in groups 2 and 4 (GMTs, 83.5 and 63.9 IU/mL, respectively; P <.0002).
This study was limited by its small sample size, its inclusion of older adults, and its short follow-up duration.
“Based on the results of this phase 1/2 trial, a phase 3, randomized, observer-blind trial is underway to compare the immunogenicity and safety of 25 mg GBP510 adjuvanted with AS03 to ChAdOx1 in adults 18 years of age and older,” the researchers concluded.
Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.
Song JY, Choi WS, Heo JY, et al. Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: a randomised, placebo-controlled, observer-blinded phase 1/2 trial. EClinicalMedicine. 2022;51:101569. doi:10.1016/j.eclinm.2022.101569