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.

Immunogenic and antigenic analysis of recombinant NSP1 and NSP11 of PRRS virus.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus in the order Nidovirales, family Arteriviridae, genus Betaarterivirus. Antibodies against nonstructural proteins (NSPs) from this virus can be found in pigs starting 4 days postinfection and they remain detectable for several months. OBJECTIVE: The goal of this study was to evaluate the immunogenicity and antigenic properties of recombinant proteins NSP1 and NSP11 expressed in Escherichia coli cells, as well as to assess the neutralization activity that they elicit. METHODS: We obtained the complete ORF-1 genes coding for NSP1 and NSP11 from PRRSV using the VR-2332 strain. Cloning was performed with the pET23a(+) vector with a histidine tag (His6), linearized by restriction enzyme digestion; the expression of the NSP1 and NSP11 clones was induced in OverExpress C41(DE3) chemically competent cells. Recombinant proteins were used to generate hyperimmune sera and we perform serological assays to confirm neutralizing antibodies. RESULTS: The expressed recombinant NSP1 and NSP11 were found to be immunogenic when injected in pigs, as well as demonstrated higher specificity in recognition of antigen in field sera from pigs positive infected with PRRSV. Furthermore, both NSP1 and NSP11 recombinant proteins elicited PRRSV neutralizing antibodies. CONCLUSIONS: In this study, we demonstrated the immune humoral response to NSP 1 and NSP11, and neutralizing-antibody response to PRRSV VR2332 strain in sera from hyperimmunized pigs.

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.

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway.

BACKGROUND: Ischemia-reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. METHODS: (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. RESULTS: (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. CONCLUSION: None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.

Evaluación de la implementación y uso de la Hoja Filtro Preconcepcional como instrumento de atención, Municipio de Tacuba, Departamento de Ahuachapán, El Salvador. 2017 / Evaluation of the implementation and use of the Preconception Filter Sheet as an instrument of attention, Municipality of Tacuba, Department of Ahuachapán, El Salvador. 2017

OBJETIVO: Evaluar la implementación y uso de la Hoja Filtro Preconcepcional como instrumento de atención, municipio de Tacuba, departamento de Ahuachapán, El Salvador, 2017. METODOLOGÍA: Estudio descriptivo, retrospectivo y de corte transversal, realizado en el municipio de Tacuba, Departamento de Ahuachapán, la unidad de análisis estuvo constituido por los expedientes clínicos y la hoja de filtro preconcepcional registrados en las ecos familiares de municipio de Tacuba correspondientes al año 2017, el universo 112 expedientes y se tomó una muestra de 76. RESULTADOS: 58 % de usuarios se encuentran siendo atendidos por médico general graduado, 56% de los establecimientos se encuentra aplicando la hoja filtro preconcepcional, solo 49 % registro factores biológicos, obstétricos y sociales; la calidad de llenado 46 % cumple totalmente con factor biológico, 46 % el factor obstétrico y 38 % el factor social, el procedimiento normatizado de seguimiento solo 15 % cumple totalmente. CONCLUSIONES Las inscripciones preconcepcionales del municipio de Tacuba fueron realizan por médico general graduado y médico en servicio social. La calidad de llenado de la hoja filtro preconcepcional no cumple con los lineamientos establecidos por el ministerio de salud. El cumplimiento del procedimiento normatizado, según el riesgo identificado por el personal de salud, no se está brindando según lo descrito en los lineamientos de Ministerio de Salud

Fecal virome composition of migratory wild duck species.

The fecal virome comprises a complex diversity of eukaryotic viruses, phages and viruses that infect the host. However, little is known about the intestinal community of viruses that is present in wild waterfowl, and the structure of this community in wild ducks has not yet been studied. The fecal virome compositions of six species of wild dabbling ducks and one species of wild diving duck were thus analyzed. Fecal samples were collected directly from the rectums of 60 ducks donated by hunters. DNA and RNA virus particles were purified and sequenced using the MiSeq Illumina platform. The reads obtained from the sequencing were analyzed and compared with sequences in the GenBank database. Viral-related sequences from the Herpesviridae, Alloherpesviridae, Adenoviridae, Retroviridae and Myoviridae viral families showed the highest overall abundances in the samples. The virome analysis identified viruses that had not been found in wild duck feces and revealed distinct virome profiles between different species and between samples of the same species. This study increases our understanding of viruses in wild ducks as possible viral reservoirs and provides a basis for further studying and monitoring the transmission of viruses from wild animals to humans and disease outbreaks in domestic animals.

Evidence of transmission and risk factors for influenza A virus in household dogs and their owners.

BACKGROUND: The possible transmission of influenza A virus between dogs and humans is important, as in Mexico City there are approximately 1·2 million dogs. We present the first evidence of influenza A virus infection in household dogs in Mexico. OBJECTIVES: The objective of this study was to identify the presence of antibodies against influenza A virus in dogs and their owners, as well as the presence of RNA of influenza A virus in nasal exudates of dogs and, thereby, assess the possible transmission of the virus between humans and dogs. METHODS: Serum samples from household dogs and their owners were analyzed to detect the presence of antibodies against three subtypes of human influenza virus (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza. We analyzed dog nasal exudates to detect influenza viral RNA. The relationship between the seropositivity of dogs and various factors (age, sex, constantly at home, and seropositivity of owners) was statistically analyzed. RESULTS: Seroprevalence for human influenza in dogs was 0·9% (1 of 113), and it was 4% (5 of 113) for equine influenza. In humans, seroprevalence was 22% for subtype H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2. No significant association (P>0·05) was found between seropositivity and any of the assessed factors. Furthermore, no viral RNA was detected in the nasal exudate samples. CONCLUSIONS: Results revealed seroprevalence of the influenza virus in household dogs in Mexico City. It can be assumed that dogs are currently becoming infected with different subtypes of influenza viruses.