Summary
Background
There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens.
Methods
This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) – and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed.
Findings
130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported.
Interpretation
Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose.
Funding
Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”.
【저자키워드】 antibodies, immune response, Neutralizing antibodies, heterologous vaccination, omicron, mRNA vaccines, BNT162b2, COVID-19 vaccines, fourth dose, CVnCoV, Boost doses of vaccines, Experimental vaccines, 【초록키워드】 COVID-19, Vaccine, vaccination, clinical trial, antibody, mRNA-1273, variant, Delta, headache, cohort study, Beta, multicentre, development, funding, Evidence, dose, Adverse reaction, anti-RBD, myalgia, Anti-RBD antibody, control group, subject, local pain, individual, regimens, participant, titre, immunogenic, finding, National, MOST, Spanish, vaccination schedule, Regional, European, benefit, neutralising, immunized, selected, reported, analysed, median, elicit, analyses, IQR, of BNT162b2, participated, severe AE, were excluded, 【제목키워드】 COVID-19 vaccine, reactogenicity, mRNA vaccine, immunization, multicenter cohort study,