Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Results of a randomized vaccine-controlled phase I ADAPTCOV trial in Brazil.

COVID-19 continues to be a health issue, mainly due to virus circulation and the emergence of new variants of concern and interest. This is a single-center, randomized, double-blind, active-controlled dose-escalating phase I clinical trial to evaluate the immunogenicity and safety of NDV-HXP-S (1 μg, 3 μg, and 10 μg), an inactivated COVID-19 vectored-vaccine virus using the Newcastle Disease Virus (NDV) expressing stabilized pre-fusion S protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthy SARS-CoV-2-naïve participants aged 18 to 59 years were randomized in a 3:3:3:1 ratio to receive two equal shots of 1 μg, 3 μg or 10 μg of NDV-HXP-S formulations or placebo/CoronaVac intramuscular 28 days apart, respectively. Primary endpoints were solicited adverse events (AEs) determined within 7 days after each dose (safety) and proportion of seroconversion and geometric mean of 50 % neutralizing titer ratios against SARS-CoV-2 Wuhan-hu-1, Beta, and Gamma strains, measured on Day 42 after the first dose (immunogenicity). Follow-up occurred for 12 months for safety and immunogenicity evaluation. This study had substantial protocol amendments, the last one for early terminating the recruitment, as well as unblinding on Day 42. We included 311 subjects were in the safety population and 301 of them (97 %) received the second dose. More frequent solicited AEs were pain at the application site (<89 %), headache (<69 %), fatigue (<68 %), and myalgia (<61 %); most were classified as mild or moderate. There was no vaccine-related serious or grade-4 solicited AE. The proportion of participants reporting a vaccine-related unsolicited AE within 28 days after each dose ranged from 30 % to 33 % after the first dose and 14 % and 18 % after the second in NDV-HXP-S, comparable to the control group. The 10 μg NDV-HXP-S formulation was the one that elicited the higher seroconversion values and neutralizing antibodies on Day 42 against SARS-CoV-2 strains. Up to 1-year follow-up, levels of bind antibodies remains about 2 log BAU/mL and no vaccine-related serious adverse event was reported. Two NDV-HXP-S shots at 10 μg elicited the higher seroconversion and neutralizing antibody titers against the SARS-CoV-2. The vaccine also displayed a very favorable safety profile. ClinicalTrials.gov,NCT04993209.