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

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 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.

VSV-Based Vaccines Reduce Virus Shedding and Viral Load in Hamsters Infected with SARS-CoV-2 Variants of Concern

“…With the encouragement of booster vaccinations, further research into novel vaccine constructs to support the demand for booster doses has been supported. Viral vector vaccines, such as the AstraZeneca ChAdOx1 nCOV/AZD1222 vaccine and the NDV-HXP-S, have shown promising results in preclinical studies and clinical application against VOC [ 19 , 20 , 21 , 22 ]. We sought to utilize the vesicular stomatitis virus (VSV)-based vaccination platform to construct a monovalent and bivalent vaccine against SARS-CoV-2.…”

Trivalent NDV-HXP-S Vaccine Protects against Phylogenetically Distant SARS-CoV-2 Variants of Concern in Mice

“…Clinical trials with a live version are ongoing in Mexico (NCT04871737) and the United States (NCT05181709), while the inactivated vaccine is being tested in Vietnam (NCT04830800), Thailand (NCT04764422), and Brazil (NCT04993209). Interim results from the initial Phase I/II trials have demonstrated that the vaccine is safe and immunogenic ( 15 – 17 ).…”

Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

“…Interim results for Phase I clinical trials of the NDV-vectored vaccine against SARS-CoV-2 have been reported using the live version in Mexico [ 79 ] and the inactivated version in Thailand [ 80 ]. The results showed both versions of the vaccine to be safe in humans.…”

“…The exclusively intranasal regime was found to generate cellular immunity but lacked a robust systemic antibody response. As such, the high-dose formulations with IM-IM and IN-IM routes were chosen for the Phase II trials [ 79 ]. As for the inactivated vaccine candidate, the immunogenicity was proportional to the dosage and was not considerably affected by the use of the adjuvant CpG 1018.…”