Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: A randomised, comparator-controlled, phase 2 trial

Abstract Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and lower-middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A public sector manufacturer in Vietnam assessed the immunogenicity of NDV-HXP-S (COVIVAC) relative to an authorized vaccine. This phase 2 stage of a randomised, observer-blind, controlled, phase 1/2 trial was conducted at three community health centers in Thai Binh Province, Vietnam. Healthy males and non-pregnant females, 18 years of age and older, were eligible. Participants were randomised by age (18–59, ≥60 years) to receive one of three treatments by intramuscular injection twice, 28 days apart: COVIVAC at 3 μg or 6 μg, or AstraZeneca COVID-19 vaccine VAXZEVRIA™. Participants and personnel assessing outcomes were masked to treatment. The vaccine dose was selected based on Phase 1 results. A 6 μg dose was chosen to explore the immunogenicity gain over the 3-μg dose. The study's aim is to evaluate the safety and immunogenicity of COVIVAC at two dose levels compared to VAXZEVRIA, the most commonly used COVID-19 vaccine in Vietnam. The main outcome was the induction of 50% neutralising antibody titers against vaccine-homologous pseudotyped virus 14 days (day 43) and 6 months (day 197) after the second vaccination by age group. The primary immunogenicity and safety analyses included all participants who received one dose of the vaccine. ClinicalTrials.govNCT05940194. During August 10–23, 2021, 737 individuals were screened, and 374 were randomised (124–125 per group); all subjects received vaccine dose one and all but three received doses two four weeks later. Subjects 18–59 years of age achieved the following geometric mean titers of PNA 14 days after vaccine dose two: 153⋅28 (95 % CI 124·2–189⋅15) for COVIVAC 3 μg, 176⋅2 (95 % CI 141⋅45–220.27) for COVIVAC 6 μg, and 99⋅92(95 % CI 80.80–123⋅56) for VAXZEVRIA. Subjects ≥60 years of age also achieved potent geometric mean titers of PNA at the same timepoint: 183⋅57 (95 % CI 133.4–252⋅61) for COVIVAC 3 μg, 257⋅87 (95 % CI 181⋅6–367⋅18) for COVIVAC 6 μg, and 79⋅49(95 % CI 55⋅68–113⋅4) for VAXZEVRIA. On day 43, the geometric mean fold rise of 50 % neutralising antibody titers for subjects age 18–59 years was 31·20 (COVIVAC 3 μg N = 82, 95 % CI 25·14–38·74), 35·80 (COVIVAC 6 μg; N = 83, 95 % CI 29·03–44·15),