Safety, Tolerability, and Immunogenicity of the TANCoV-1.3.20 SARS-CoV-2 Vaccine Among Healthy Participants in Tanzania: Protocol for a Multisite, Phase 1/2a, Double-Blinded Randomized Controlled Trial.

Background: The COVID-19 pandemic has caused devastating morbidity and mortality globally, and poses an unprecedented threat to economic growth. The global rollout of vaccines has been met with socioeconomic disparities, impeding the global effort in infection prevention and severity reduction. The development and evaluation of candidate vaccines against COVID-19 that overcome logistical, social, and economic challenges are highly needed. Here, a trial protocol is presented to assess the safety, tolerability, and immunogenicity of the TANCoV-1.3.20 SARS-CoV-2 vaccine among healthy participants who were SARS-CoV-2 negative in Tanzania. Objective: The primary objective of this study was to evaluate the safety and tolerability of the TANCoV-1.3.20 nasal SARS-CoV-2 vaccine in healthy adult participants in Tanzania. The secondary objectives included the assessment of vaccine-induced humoral and cellular immune responses, and preliminary evaluation of dose-related immunogenicity. Methods: TANCoV-1 is a phase 1/2a double-blinded, randomized controlled trial conducted in the Dar es Salaam and Mbeya regions of Tanzania. A total of 150 healthy participants were planned to be recruited and randomized at a 1:1:1 ratio to receive a TANCoV-1.3.20 vaccination dose of 100 µL with or without a booster, or 200 µL without a booster. Each dose group was planned to contain an intervention arm and a control arm in a 1:1 ratio. In general, 75 participants were planned to be assigned to the experimental arm, and another 75 participants were planned to be assigned to the standard arm. Participant recruitment was expected to take 6 months, with follow-up for 6 months post vaccination. The trial has two primary end points: (1) safety, as ascertained by the incidence of adverse events, and (2) immunogenicity, which involves local, humoral, and cellular immune responses. The trial enrolled healthy individuals aged between 18 and 45 years, who provided written informed consent and met all the inclusion criteria per the protocol. The data will be analyzed using Stata (version 14; StataCorp LLC). Findings will be reported according to the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Results: This paper describes the study protocol. Recruitment was completed in February 2024, following regulatory and ethical approvals. Safety and immunogenicity data will be analyzed after the completion of participants' follow-ups. Laboratory testing is ongoing, and data cleaning and statistical analyses are underway. Safety and immunogenicity outcomes will be analyzed after all follow-up visits and laboratory assays have been completed. Conclusions: This randomized clinical trial in an African context will provide valuable data that can be used to ensure the future availability of safe, cost-effective, and environmentally accustomed effective vaccines. Furthermore, the findings of this trial will help increase public awareness and acceptance of COVID-19 vaccines, contributing to efforts to combat the COVID-19 pandemic.