Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial

Innis, B. L.; Mercer, L. D.; White, J. A.; Scharf, R.; Hjorth, R.; Lamola, S.; Raghunandan, R.; Lal, M.; McLellan, J. S.; Hsieh, C.-L.; Pitisuttithum, P.; Luvira, V.; Muangnoicharoen, S.; Lawpoolsri, S.; Sivakorn, C.; Phumratanaprapin, W.; Kamolratanakul, S.; Phonrat, B.; Sabmee, Y.; Thantamnu, N.; Wirachwong, P.; Poopipatpol, K.; Surichan, S.; Prangpratanporn, S.; Kaweepornpoj, R.; Theerasurakarn, S.; Narakorn, P.; Singchareon, R.; Suthepakul, N.; Puksuriwong, S.; Vilasmongkolchai, T.; Gagnon, L.; Tran, S.; Khan, S.; Krammer, F.; Mena, I.; Garcia-Sastre, A.; Sun, W.; Liu, Y.; McCroskery, S.

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 microgram (mcg) +/- CpG1018 (a toll-like receptor 9 agonist), 3 mcg +/- CpG1018, 10 mcg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5.7% to 17.1% among vaccine groups and was 2.9% in controls; there was no vaccine-related serious adverse event. The immunogenicity of the 10 mcg formulation ranked best, followed by 3 mcg+CpG1018, 3 mcg, 1 mcg+CpG1018, and 1 mcg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122.23 IU/mL (1 mcg, 95% CI 86.40-172.91) to 474.35 IU/mL (10 mcg, 95% CI 320.90-701.19), with 93.9% to 100% of vaccine groups attaining a => 4-fold increase over baseline. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 mcg and 3 mcg+CpG1018 formulations advanced to phase 2.