A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

Continuous evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and monoclonal antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S subunit, which folds as a spring-loaded fusion machinery. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S subunit and high yield recombinant expression of trimers with native structure and antigenicity.

Adjuvant-dependent effects on the safety and efficacy of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease.

Targeting spike glycans to inhibit SARS-CoV2 viral entry.

SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans.

Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2.

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice.

Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

Unlabelled: The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice.

A broadly neutralizing antibody protects against SARS-CoV, pre-emergent bat CoVs, and SARS-CoV-2 variants in mice.

SARS-CoV in 2003, SARS-CoV-2 in 2019, and SARS-CoV-2 variants of concern (VOC) can cause deadly infections, underlining the importance of developing broadly effective countermeasures against Group 2B Sarbecoviruses, which could be key in the rapid prevention and mitigation of future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV, bat CoVs WIV-1 and RsSHC014, and SARS-CoV-2 variants D614G, B.1.

Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice.

Improving the standard of clinical care for individuals infected with SARS-CoV-2 variants is a global health priority. Small molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, it is not known if combination RDV/mAb will improve outcomes over single agent therapies or whether antibody therapies will remain efficacious against variants.

A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine.

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters.

Access and use of oxytocin for postpartum haemorrhage prevention: a pre-post study targeting the poorest in six Mesoamerican countries.

Objectives: Haemorrhage remains the leading cause of maternal mortality in Central America. The Salud Mesoamérica Initiative aims to reduce such mortality via performance indicators. Our objective was to assess the availability and administration of oxytocin, before and after applying Salud Mesoamérica Initiative interventions in the poorest health facilities across Central America.

Antenatal care as a means to increase participation in the continuum of maternal and child healthcare: an analysis of the poorest regions of four Mesoamérican countries.

Background: Antenatal care (ANC) is a means to identify high-risk pregnancies and educate women so that they might experience a healthier delivery and outcome. There is a lack of evidence about whether receipt of ANC is an effective strategy for keeping women in the system so they partake in other maternal and child interventions, particularly for poor women. The present analysis examines whether ANC uptake is associated with other maternal and child health behaviors in poor mothers in Guatemala, Honduras, Nicaragua, and Mexico (Chiapas).

Results-based aid with lasting effects: sustainability in the Salud Mesoamérica Initiative.

Background: The Salud Mesoamérica Initiative is a public-private partnership aimed at reducing maternal and child morbidity and mortality for the poorest populations in Central America and the southernmost state of Mexico. Currently at the midpoint of implementation and with external funding expected to phase out by 2020, SMI's sustainability warrants evaluation. In this study, we examine if the major SMI components fit into the Dynamic Sustainability Framework to predict whether SMI benefits could be sustainable beyond the external funding and to identify threats to sustainability.

Methods to measure quality of care and quality indicators through health facility surveys in low- and middle-income countries.

Objective: Present methods to measure standardized, replicable and comparable metrics to measure quality of medical care in low- and middle-income countries.

Design: We constructed quality indicators for maternal, neonatal and child care. To minimize reviewer judgment, we transformed criteria from check-lists into data points and decisions into conditional algorithms.

Appropriate and timely antibiotic administration for neonatal sepsis in Mesoamérica.

Neonatal sepsis is a leading cause of mortality among children under-5 in Latin America. The Salud Mesoamérica Initiative (SMI), a multicountry results-based aid programme, was designed to improve maternal, newborn and child health in impoverished communities in Mesoamérica. This study examines the delivery of timely and appropriate antibiotics for neonatal sepsis among facilities participating in the SMI project.

Supply-side interventions to improve health: Findings from the Salud Mesoamérica Initiative.

Background: Results-based aid (RBA) is increasingly used to incentivize action in health. In Mesoamerica, the region consisting of southern Mexico and Central America, the RBA project known as the Salud Mesoamérica Initiative (SMI) was designed to target disparities in maternal and child health, focusing on the poorest 20% of the population across the region.

Methods And Findings: Data were first collected in 365 intervention health facilities to establish a baseline of indicators.

Healthy competition drives success in results-based aid: Lessons from the Salud Mesoamérica Initiative.

Objectives: The Salud Mesoamérica Initiative (SMI) is a three-operation strategy, and is a pioneer in the world of results-based aid (RBA) in terms of the success it has achieved in improving health system inputs following its initial operation. This success in meeting pre-defined targets is rare in the world of financial assistance for health. We investigated the influential aspects of SMI that could have contributed to its effectiveness in improving health systems, with the aim of providing international donors, bilateral organizations, philanthropies, and recipient countries with new perspectives that can help increase the effectiveness of future assistance for health, specifically in the arena of RBA.

Perceptions of and barriers to family planning services in the poorest regions of Chiapas, Mexico: a qualitative study of men, women, and adolescents.

Background: In the poorest regions of Chiapas, Mexico, 50.2% of women in need of contraceptives do not use any modern method. A qualitative study was needed to design effective and culturally appropriate interventions.

Barriers and facilitators for institutional delivery among poor Mesoamerican women: a cross-sectional study.

Professional skilled care has shown to be one of the most promising strategies to reduce maternal mortality, and in-facility deliveries are a cost-effective way to ensure safe births. Countries in Mesoamerica have emphasized in-facility delivery care by professionally skilled attendants, but access to good-quality delivery care is still lacking for many women. We examined the characteristics of women who had a delivery in a health facility and determinants of the decision to bypass a closer facility and travel to a distant one.

Institutional Delivery and Satisfaction among Indigenous and Poor Women in Guatemala, Mexico, and Panama.

Indigenous women in Mesoamerica experience disproportionately high maternal mortality rates and are less likely to have institutional deliveries. Identifying correlates of institutional delivery, and satisfaction with institutional deliveries, may help improve facility utilization and health outcomes in this population. We used baseline surveys from the Salud Mesoamérica Initiative to analyze data from 10,895 indigenous and non-indigenous women in Guatemala and Mexico (Chiapas State) and indigenous women in Panama.

Diarrhea Prevalence, Care, and Risk Factors Among Poor Children Under 5 Years of Age in Mesoamerica.

Care practices and risk factors for diarrhea among impoverished communities across Mesoamerica are unknown. Using Salud Mesoamérica Initiative baseline data, collected 2011-2013, we assessed the prevalence of diarrhea, adherence to evidence-based treatment guidelines, and potential diarrhea correlates in poor and indigenous communities across Mesoamerica. This study surveyed 14,500 children under 5 years of age in poor areas of El Salvador, Guatemala, Mexico (Chiapas State), Nicaragua, and Panama.

Health and wealth in Mesoamerica: findings from Salud Mesomérica 2015.

Background: Individual income and poverty are associated with poor health outcomes. The poor face unique challenges related to access, education, financial capacity, environmental effects, and other factors that threaten their health outcomes.

Methods: We examined the variation in the health outcomes and health behaviors among the poorest quintile in eight countries of Mesoamerica using data from the Salud Mesomérica 2015 baseline household surveys.

Breastfeeding Practices among Poor Women in Mesoamerica.

Background: Breastfeeding is an effective intervention to reduce pediatric morbidity and mortality. The prevalence of practices and predictors of breastfeeding among the poor in Mesoamerica has not been well described.

Objectives: We estimated the prevalence of ever breastfeeding, early initiation of breastfeeding, exclusive breastfeeding, and breastfeeding between 6 mo and 2 y of age using household survey data for the poorest quintile of families living in 6 Mesoamerican countries.