Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico

Abstract

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

A Phase II Study Integrating a Single-Blind Safety Phase with a Double-Blind, Placebo-Controlled Randomized Phase, Assessing Single-Dose Intramuscular or Intranasal Administration to Evaluate the Safety and Immunogenicity of the Recombinant Vaccine Against COVID-19 (AVX/COVID-12 “Patria”) Based on an Active Newcastle Disease Viral Vector as a Heterologous Booster in Subjects with Evidence of Previous Immunity to SARS-CoV-2

“…Three 50% embryo infective doses (EID50%) (Low: 10 7.0 EID50%, Middle: 10 7.5 EID50% or High: 10 8.0 EID50%) were well-tolerated, with minimal reactogenicity. No serious adverse events were associated with any route or dose, confirming the vaccine’s safety and immunogenic profile (12). The study laid the foundation for subsequent clinical development.…”

Phase II/III Double-Blind Study Evaluating Safety and Immunogenicity of a Single Intramuscular Booster Dose of the Recombinant SARS-CoV-2 Vaccine “Patria” (AVX/COVID-12) Using an Active Newcastle Disease Viral Vector (NDV) during the Omicron Outbreak in Healthy Adults with Elevated Baseline Antibody Titers from Prior COVID-19 and/or SARS-CoV-2 Vaccination

“…Furthermore, the nature, incidence, and severity of adverse events recorded during this study do not indicate any alarming signals following the administration of the AVX/COVID-12 vaccine. The demonstrated safety of the AVX/COVID-12 vaccine aligns with the outcomes of earlier clinical phases (11,16).…”

“…In a Phase I clinical trial (NCT04871737) with 91 volunteers, the vaccine was evaluated with various booster regimens administered through both IM and IN routes, demonstrating significant immunogenicity in both cases. The safety of this vaccine was also confirmed in these studies, establishing the foundation for further clinical development (11).…”

Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate AVX/COVID-12 Activates T Cells and Is Recognized by Antibodies from COVID-19 Patients and Vaccinated

“…This vaccine has demonstrated safety, immunogenicity, and protective efficacy in preclinical models (5,6), and has the advantage of being produced in embryonated egg industrial facilities similarly to influenza vaccine production which is cheap and widely available (7). In a phase I clinical trial, the AVX/COVID-12 vaccine demonstrated safety, good tolerability, and immunogenicity in volunteers (8), supporting further clinical development of the vaccine. However, high rates of infections in the population and the availability of approved vaccines in Mexico made the development of a phase II placebo-controlled clinical trial unethical.…”