RESUMO

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Assuntos

Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Ativação Linfocitária , Vírus da Doença de Newcastle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Vírus da Doença de Newcastle/imunologia , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Ativação Linfocitária/imunologia , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacina BNT162/imunologia , Vacinação , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo

RESUMO

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.

RESUMO

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.

RESUMO

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.

Assuntos

Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vírus da Doença de Newcastle/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Formação de Anticorpos/fisiologia , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Suínos

RESUMO

Identifying animals as sentinels for humans and other animal species is an excellent method for understanding exposure to environmental contamination at different times and places. Shorebirds are useful sentinels because they have a world-wide distribution, eat a range of prey, and are eaten by a range of other species, including humans. We collected blood from semipalmated sandpipers (Calidris pusilla) wintering in northern (Suriname N = 71) and northeastern (Brazil N = 61) South America to examine levels of heavy metals and metalloids (arsenic, selenium), and compare them to blood levels in sandpipers at a heavily used stopover site in New Jersey (N = 30; Delaware Bay, NJ). Since blood represents relatively recent exposure, it can provide information on where and when the birds were exposed. Levels were highest in Brazil for arsenic and particularly selenium; highest in Suriname for cadmium and lead; and highest in New Jersey for chromium. Samples from Brazil and Suriname presented higher levels of mercury than did those from New Jersey. There were no geographic differences for cobalt. Levels of all metals were generally within an order of magnitude. The significant geographic difference for selenium was interesting because it is regulated in the body. Selenium levels in the NJ sample were directly proportional to levels found in their principle food at this migration stopover site (eggs of horseshoe crab, Limulus polyphemus). Mean selenium level was almost an order of magnitude higher in the semipalmated sandpiper blood samples from Brazil (mean of 27,500 µg/L= ppb) compared to the other sampling locations (mean > 5330 µg/L). This is a toxic level and cause for concern and further investigation, alerting us to look for other evidence of excess selenium exposure. Otherwise the levels of other metals are generally not high enough to cause harm to the sandpipers themselves or to predators that eat them. We discuss the implications for these birds and their exposure to contaminants at different stopover sites.

Assuntos

Aves/sangue , Monitoramento Ambiental , Poluentes Ambientais/sangue , Metais/sangue , Selênio , Animais , Baías , Brasil , Delaware , New Jersey , Suriname

RESUMO

It is essential to understand contaminant exposure and to compare levels of contaminants in organisms at different ages to determine if there is bioaccumulation, and to compare levels encountered in different geographical areas. In this paper, we report levels of mercury, lead, cadmium, cobalt, arsenic and selenium in the blood of semipalmated sandpipers (Calidris pusilla) wintering in Suriname as a function of age, and compare them to blood levels in northbound migrants at a stopover in Delaware Bay, New Jersey. We found (1) young birds had higher levels of cadmium, cobalt, and lead than adults (after second year birds); (2) there were no age-related differences for arsenic, mercury and selenium; (3) only four of the possible 16 inter-metal correlations were significant, at the 0.05 level; (4) the highest correlation was between cadmium and lead (Kendall tau = 0.37); and (5) the adult sandpipers had significantly higher levels of cadmium, mercury and selenium in Suriname than in New Jersey, while the New Jersey birds had significantly higher levels of arsenic. Suriname samples were obtained in April, after both age classes had spent the winter in Suriname, which suggests that sandpipers are accumulating higher levels of trace elements in Suriname than in Delaware Bay. The levels of selenium may be within a range of concern for adverse effects, but little is known about adverse effect levels of trace elements in the blood of wild birds.