Results
infection, rhinorrhoea
ADVERSE REACTIONS, ADVERSE EVENTS, ADVERSE EVENT, DISEASE, ASYMPTOMATIC SARS-COV-2 INFECTION, MAY, INFECTION, BLIND
Between Dec 16, 2021, and May 31, 2022, 41 620 participants were screened for eligibility, of whom 31 038 were enrolled and randomly assigned (17 210 with a history of SARS-CoV-2 vaccination and 13 828 without; 15 517 in the vaccine group and 15 521 in the placebo group). 30 990 participants received at least one dose of the vaccine or placebo, including 17 176 participants with a history of SARS-CoV-2 vaccination and 13 814 participants without (Trial profile*The 384 Colombian participants without previous SARS-CoV-2 vaccinations who received at least one dose were excluded from the primary efficacy analysis during the blind data review meeting for this trial because the sample size from each site was too small. †An addendum was made to the protocol to permit the enrolment of individuals in Viet Nam who received their last vaccine dose 3–6 months before signing the informed consent because of the ongoing national SARS-CoV-2 vaccine booster campaign, but these participants were not included in the primary efficacy analysis. ‡Eight participants had vaccination errors. Five participants (four with previous SARS-CoV-2 vaccinations and one without) were assigned to the placebo group but received at least one dose of dNS1-RBD, and were included in the vaccine group for the safety analysis; one participant without previous SARS-CoV-2 vaccinations who was assigned to the vaccine group but received two doses of placebo was included in the placebo group for the safety analysis; and two participants with previous SARS-CoV-2 vaccinations who were assigned to the vaccine group but received one dose of placebo and one dose of vaccine were included in the vaccine group for the safety analysis.Extreme difficulty in recruiting participants without previous SARS-CoV-2 vaccination in Colombia resulted in a smaller sample size than initially planned. 389 participants without a SARS-CoV-2 vaccination history were enrolled from eight centres (sample size range 4–159) who received at least one dose in this trial. A small sample size in each centre in Colombia might have resulted in additional uncertainties and confounding factors between treatment groups when the incidence of target disease is extremely high and fluctuates rapidly, and the independent randomisation done at each centre might lead to an uneven distribution of participant characteristics across the groups. In addition to the small sample size, there was also an increased possibility of false negative SARS-CoV-2 antibodies results at baseline due to an omicron (BA.1 and BA.2) outbreak in the country before enrolment. Because of the small sample size and possibility of false negatives, 389 Colombian participants (including eight participants with confirmed COVID-19) were excluded from all efficacy analyses (five of them were excluded firstly because they did not receive the second dose; The median efficacy follow-up was 161 days (IQR 111–189), with an overall dropout rate of 2·2% (668/30 990) and no significant differences between the two groups (Demographic and baseline characteristics in participants who received at least one doseData are median (IQR) or n (%). Percentages might not total 100% because of rounding.Participants who received at least one dose of vaccine or placebo, based on randomised grouping information, not adjusted for actual administrations (ie, without correcting for vaccination errors).Undifferentiated sex means that sex cannot be determined on the basis of physiological characteristics.Underlying chronic conditions were those that were ongoing at baseline and could increase the risk of SARS-CoV-2 infection.30 participants had a positive test result for SARS-CoV-2 antibodies but were accidentally enrolled and categorised as participant without a SARS-CoV-2 vaccination history.30 990 participants were included in the safety analysis set. Overall, adverse reactions including local and systemic were largely absent or mild (ie, about 96% of adverse reactions were grade 1 or 2; Adverse events and reactions that occurred after any dose in the safety populationData are n (%), unless otherwise stated. Any refers to all participants with any grade of adverse events or reactions. NA=not applicable.Participants who received at least one dose of vaccine or placebo, based on actual administrations.Among all vaccine recipients, the most commonly reported local solicited adverse reactions were rhinorrhoea (578 [3·7%] of 15 500 participants in the vaccine group Solicited local and systemic adverse reactions that occurred within 7 days after any dose in the safety population*Incidence and severity of local and systemic adverse reactions in participants without a previous SARS-CoV-2 vaccination history (A) and in those with a SARS-CoV-2 vaccination history (B). All adverse reactions were graded according to the China National Medical Products Administration guidelines. *Participants who received at least one dose of vaccine or placebo.No difference was observed in the occurrence of adverse events and reactions between participants in the vaccine and placebo groups in all prespecified subgroups, including older recipients (aged ≥60 years) and participants with underlying chronic conditions at baseline (Among the 30 290 participants who received two doses, 25 742 were included in the per-protocol population for efficacy analysis (Regarding the primary efficacy endpoint, regardless of baseline immunisation history, the two-dose vaccine efficacy in the per-protocol population against confirmed symptomatic SARS-CoV-2 infections during the efficacy observation period was 28·2% (95% CI 3·4 to 46·6; Vaccine efficacy 15 days or more after the second dose in the per-protocol population* and in the modified intention-to-treat population†The vertical line at 30% shows the prespecified vaccine efficacy target. *Participants who received two doses of vaccine or placebo, were followed up for 15 days or longer after the second dose, and had no major protocol deviations. †Participants who received two doses of vaccine or placebo and were followed up for 15 days or longer after the second dose.During the efficacy observation period, five participants in the placebo group (none in the vaccine group) were hospitalised (WHO score ≥4) with onset at any time after the first dose (In a post-hoc analysis of individuals with more typical symptomatic SARS-CoV-2 infections who reported three or more suspected symptoms (omicron symptom index ≥3), 125 participants were included (47 in the vaccine group and 78 in the placebo group). Among participants in the per-protocol population, the vaccine efficacy against typical symptomatic SARS-CoV-2 infections during the efficacy observation period (≥15 days) was 39·6% (95% CI 13·3 to 57·9), whereas the efficacy within 3 months (15–90 days) of the second dose was 42·3% (15·7 to 60·5). During the efficacy observation period, vaccine efficacy against typical infection was 56·3% (–6·3 to 82·0) in participants without a SARS-CoV-2 vaccination history and 35·1% (3·4 to 56·4) in those with a SARS-CoV-2 vaccination history (