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

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.

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.

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.

Safety and Immunogenicity of a Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate, AVX/COVID-12-HEXAPRO (Patria), in Pigs.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed in record time and show excellent efficacy and effectiveness against coronavirus disease 2019 (COVID-19). However, currently approved vaccines cannot meet the global demand. In addition, none of the currently used vaccines is administered intranasally to potentially induce mucosal immunity. Here, we tested the safety and immunogenicity of a second-generation SARS-CoV-2 vaccine that includes a stabilized spike antigen and can be administered intranasally. The vaccine is based on a live Newcastle disease virus vector expressing a SARS-CoV-2 spike protein stabilized in a prefusion conformation with six beneficial proline substitutions (AVX/COVID-12-HEXAPRO; Patria). Immunogenicity testing in the pig model showed that both intranasal and intramuscular application of the vaccine as well as a combination of the two induced strong serum neutralizing antibody responses. Furthermore, substantial reactivity to B.1.1.7, B.1.351, and P.1 spike variants was detected. Finally, no adverse reactions were found in the experimental animals at any dose level or delivery route. These results indicate that the experimental vaccine AVX/COVID-12-HEXAPRO (Patria) is safe and highly immunogenic in the pig model. IMPORTANCE Several highly efficacious vaccines for SARS-CoV-2 have been developed and are used in the population. However, the current production capacity cannot meet the global demand. Therefore, additional vaccines-especially ones that can be produced locally and at low cost-are urgently needed. This work describes preclinical testing of a SARS-CoV-2 vaccine candidate which meets these criteria.

Protective dose of a recombinant Newcastle disease LaSota-avian influenza virus H5 vaccine against H5N2 highly pathogenic avian influenza virus and velogenic viscerotropic Newcastle disease virus in broilers with high maternal antibody levels.

The protective dose of a live recombinant LaSota Newcastle disease virus (NDV)-avian influenza H5 vaccine (rNDV-LS/AI-H5) was determined in broiler chickens with high levels of maternal antibodies against NDV and avian influenza virus (AIV). At hatch the geometric mean titers (GMT) of the chickens' maternal antibodies were 2(5.1) and 2(10.3) for NDV and AIV, respectively. At the time of vaccination the GMT was 2(3.1) for NDV and 2(7.9) for AIV. The chickens were vaccinated with one drop (0.03 ml) in the eye at 10 days of age as is typical under field conditions. The test chickens received 10(4.8), 10(5.8), 10(6.8), or 10(7.8) mean chicken embryo infective doses (CEID50) of the rNDV-LS/AI-H5 vaccine. Control chickens were either nonvaccinated, or vaccinated with 10(5.8) or 10(6.8) CEID50 of a commercial live LaSota NDV vaccine. Birds were challenged with either the Mexican highly pathogenic avian influenza virus (HPAIV) strain A/Chicken/Queretaro/14588-19/95 (H5N2) or a Mexican velogenic viscerotropic (VV) NDV strain. One hundred percent of the chickens vaccinated with the rNDV-LS/AI-H5 vaccine were protected against HPAIV and VVNDV when a challenge dose of 10(6.8) EID50 or higher was administered by eye drop. Birds vaccinated with the LaSota NDV vaccine were protected against VVNDV, but not against HPAIV.

Protection and differentiation of infected from vaccinated animals by an inactivated recombinant Newcastle disease virus/avian influenza H5 vaccine.

Specific-pathogen-free chickens immunized at 14 days of age with either an inactivated recombinant Newcastle disease virus-LaSota/avian influenza H5 (K-rNDV-LS/AI-H5) vaccine or a killed Newcastle disease/avian influenza whole-virus vaccine (K-ND/AI) were protected from disease when challenged with either A/chicken/Queretaro/14588-19/95 (H5N2), a high pathogenicity avian influenza virus (HPAIV) strain isolated in Mexico in 1995, or with a Mexican velogenic viscerotropic Newcastle disease virus (VVNDV) strain 21 days postvaccination. All nonvaccinated chickens challenged with HPAIV or VVNDV succumbed to disease, while those vaccinated with K-rNDV-LS/AI-H5 or K-ND/AI were protected from severe clinical signs and death. Both vaccines induced hemagglutination-inhibition (HI) antibody responses against NDV and AIV. Antibodies against AIV nucleoprotein were not detected by enzyme-linked immunosorbent assay (ELISA) in birds vaccinated with the inactivated rNDV-LS/AI-H5 vaccine. These chickens became positive for AIV antibodies by ELISA only after challenge with HPAIV. The data clearly indicate that the inactivated rNDV-LS/AI-H5 vaccine confers protection comparable to that of the conventional killed whole-virus vaccine against both NDV and AIV, while still allowing differentiation of infected from vaccinated animals by HI and ELISA tests.