The global inequity in the distribution of COVID-19 vaccines underscores the urgent need for innovative and cost-effective vaccine technologies to address access disparities and implement local manufacturing capabilities. This is essential for achieving and sustaining widespread immunity, and for ensuring timely protection of vulnerable populations during future booster campaigns in lower- middle income countries (LMICs). To address this need, we conducted a phase II clinical trial to evaluate the safety and immunogenicity of the locally manufactured AVX/COVID-12 "Patria" (AVX) vaccine as a booster dose. The vaccine was administered either intramuscularly (IM) or intranasally (IN) to participants who had previously completed a vaccination regimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using adenoviral vector, inactivated virus, or mRNA-based vaccines. Participants with initial anti-spike IgG titers below 1,200 U/mL were included, allowing us to observe the booster effect induced by vaccination. Both IM and IN immunization with AVX were found to be safe and well-tolerated. The vaccine induced a significant (>2.5-fold) increase in neutralizing antibodies against the ancestral Wuhan strain and variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron (BA.2 and BA.5). This immune response was further supported by increased cellular production of interferon-gamma (IFN-γ), demonstrating a robust and multifaceted immune reaction. The administration of AVX as a booster dose, whether through IM or IN routes, was safe and well-tolerated. The vaccine extended immune responses not only against the ancestral 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.

Species A rotavirus non-structural protein 3 (NSP3) is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A) binding protein (PABP) from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3’-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD). We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E), whereas one mutation had the opposite effects (Y192A). Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

Background: An NDV-based vector has been used as a veterinary vaccine and, recently, as a human COVID-19 vaccine. However, data for the potential immune response against the vector in humans are scarce; therefore, it is important to evaluate the levels of antibodies produced. The HI assay is the gold standard for assessing the humoral response against NDV in poultry serum. Objective: Here, the objective was to validate the HI assay against the NDV-vectored vaccine to analyze antibodies in human serum. Methods: First, we standardized the conditions in human sera before validation. Results: The results for analytical performance in terms of selectivity, sensitivity, specificity, and positive and negative predictive values, as well as positive and negative diagnostic reliability, indicate that the assay is highly selective, allowing clear discrimination between positive and negative samples. Regarding repeatability and intermediate precision, we demonstrated that the assay has the precision to obtain consistent results, guaranteeing their reliability and truthfulness. Finally, the results regarding accuracy, linearity, and robustness indicate that the assay is accurate across the evaluated concentration intervals, with a linear correlation between low and high levels, and demonstrate that it is robust and consistent when serum–antigen interaction times are changed. Conclusions: We conclude that the suitability of the analytical method for its intended use is confirmed, guaranteeing the reliability of the results obtained under the established operating conditions.

NDV-based vector has been used as a veterinary vaccine and, recently also for human COVID-19 vaccine; however, data about the potential immune response against vector in humans is scarce, therefore, it is important evaluate levels of antibodies produced. The HI assay is the gold standard for assessing the humoral response against NDV in poultry serum. Here the objective of was validate the HI assay against the NDV-vectored vaccine to analyze antibodies in human serum. First, we standardized conditions in human sera before validation. The results from analytical performance: selectivity, sensitivity, specificity, positive and negative predictive value, as well as positive and negative diagnostic reliability, indicate that the assay is highly selective, as it allows clear discrimination between positive and negative samples. Regarding repeatability and inter-mediate precision, we demonstrated that the assay has precision to obtain consistent results and guarantees their reliability and truthfulness. Finally, the results of accuracy, linearity and robustness, indicate that the assay is accurate at the concentration intervals evaluated with a linear correlation between the low and high level and demonstrated that it is robust and consistent when the serum-antigen interaction times changed. We conclude that the suitability of the analytical method for its intended use is confirmed and guarantees the reliability of the results obtained under the established operating conditions.

In countries with suboptimal vaccination coverage, human papillomavirus (HPV) genital infections remain a public health problem. Furthermore, the prevalence of specific HPV genotypes in unvaccinated women is uncertain. Therefore, this study aimed to retrospectively evaluate HPV prevalence and genotype distribution among unvaccinated women attending a gynaecology and obstetrics hospital in Mexico, and to establish potential associations between HPV infection and the different pathologies affecting unvaccinated women. A single-centre, retrospective analysis of 347 unvaccinated women who underwent gynaecological examination and had an HPV test was conducted. HPV genotypes in cervical cells were determined using the CLART HPV4 system, which can detect 35 HPV genotypes. Overall, 124 (35.73%) women tested positive for HPV, which included single- and multiple-genotype infections. Oncogenic, high-risk HPV (HR-HPV) genotypes were detected in 74.19% of the HPV-positive women. Ranked by prevalence, HPV59 was the most frequent, followed by HPV16, HPV39, HPV31, and HPV42. Out of the 11 HR-HPV genotypes identified, 6 are targeted by the nonavalent HPV vaccine. In conclusion, this study reports the prevalence of HPV infection among unvaccinated women attending a gynaecological and obstetric centre and demonstrates that HR-HPV genotypes are the most prevalent in this population. These data may facilitate the design of organised screening and vaccination programmes to reduce genital infection and cervical cancer burden in México.