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. (preprint)

BackgroundThe global inequity in coronavirus disease 2019 (COVID-19) vaccine distribution, primarily affecting low- and middle-income countries (LMICs), highlights the urgent need for innovative and cost-effective vaccine technologies to address availability disparities. This is crucial for achieving and sustaining widespread immunity and protecting vulnerable populations during future booster campaigns. MethodsTo address this need, we conducted a phase II clinical trial evaluating the safety and immunogenicity of the AVX/COVID-12 "Patria" vaccine as a booster dose. The vaccine was administered through both intramuscular (IM) and intranasal (IN) routes to participants who had previously received severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on adenoviral technology, inactivated virus, or mRNA technology. The inclusion criterion involved individuals with initial anti-spike IgG titers below 1,200 U/mL, allowing observation of the booster effect induced by vaccination. ResultsImmunization with AVX/COVID-12 resulted in a significant (>2.5 times) increase in neutralizing antibodies against the original Wuhan strain and variants of concern (VOCs) such as Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was accompanied by cellular interferon-gamma (IFN-{gamma}) production, indicating a robust and multifaceted reaction. ConclusionsThe administration of AVX/COVID-12 as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the original Wuhan-1 strain but also against various VOCs. Its ability to enhance preexisting immune responses suggests a potential contribution to expanding and sustaining herd immunity within the population.

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico (preprint)

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 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. Funding was provided by Avimex and CONACYT.