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SUMMARYThe emergence of three distinct highly pathogenic human coronaviruses – SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019 – underlines the need to develop broadly active vaccines against theMerbecovirusandSarbecovirusbetacoronavirus subgenera. While SARS-CoV-2 vaccines are highly protective against severe COVID-19 disease, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor binding domains (RBDs), which elicited live-virus neutralizing antibody responses and broad protection. Specifically, a monovalent SARS-CoV-2 RBD scNP vaccine only protected against sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both merbecovirus and sarbecovirus challenge in highly pathogenic and lethal mouse models. Moreover, the trivalent RBD scNP elicited serum neutralizing antibodies against SARS-CoV, MERS-CoV and SARS-CoV-2 BA.1 live viruses. Our findings show that a trivalent RBD nanoparticle vaccine displaying merbecovirus and sarbecovirus immunogens elicits immunity that broadly protects mice against disease. This study demonstrates proof-of-concept for a single pan-betacoronavirus vaccine to protect against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.

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. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice.ImportanceWe have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.

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.1.1.7, B.1.429, B1.351 by a receptor-binding domain (RBD)-specific antibody DH1047. Prophylactic and therapeutic treatment with DH1047 demonstrated protection against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B1.351infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among Sarbecoviruses. We conclude that DH1047 is a broadly neutralizing and protective antibody that can prevent infection and mitigate outbreaks caused by SARS-like strains and SARS-CoV-2 variants. Our results argue that the RBD conserved epitope bound by DH1047 is a rational target for pan Group 2B coronavirus vaccines.

Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.Research in contextEvidence before this studyThe spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles virus and Modified vaccinia Ankara.Added value of this studyThe NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine.Implications of all the available evidenceThis study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.

SUMMARYThe Coronavirus Disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of systemic and mucosal IgA and T cell responses, completely prevents SARS-CoV-2 infection in the upper and lower respiratory tracts, and likely confers sterilizing immunity in most animals. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.

Correlophus ciliatus (Crested Geckos) are a gecko species found in the pet trade and in zoological institutions. Native to New Caledonia and once thought to be extinct, C. ciliatus now thrive in human care due to husbandry and subsequent ease of breeding in managed facilities. There are multiple discrepancies in best practices of how to properly house C. ciliatus, specifically females. It is commonly known that males are aggressive towards one another, and it is common practice to house females together in one enclosure to their perceived lack of aggression towards conspecifics. In an effort to increase welfare for female C. ciliatus, we conducted an ethnographic analysis of female C. ciliatus cohabitated in human care. We placed two sets of three female C. ciliatus in a vivarium, videoed each respective cohort of females for 60 days, defined behaviors, and attempted to determine if dominance behavior were exhibited by females through ethnographic analysis. Chi-Square tests were used to determine if any identified behaviors occurred more frequently than others for each respective female and also what zone did we see the most aggressive behaviors in the enclosure. In each set, we found that there was one dominant female with two submissive conspecifics.

Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2. Herein, we show that the ribonucleoside analog β-D-N4-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV 2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to another nucleoside analog inhibitor. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (b-D-N4-hydroxycytidine-5’-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis. The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

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. We used baseline information from the Salud Mesoamerica Initiative (SMI). Data were collected from a large household and facilities sample in the poorest quintile of the population in Guatemala, Honduras and Nicaragua. The analysis included 1592 deliveries. After controlling for characteristics of women and health facilities, being primiparous (RR = 1.15, 95% CI 1.10, 1.21), being literate (RR = 1.24, 95% CI 1.04, 1.48), having antenatal care (RR = 1.68, 95% CI 1.24, 2.27), being informed of the need for having a C-section (RR = 1.07, 95% CI 1.02, 1.11) and travel time to the closest facility totaling 1-2 h vs under 30 min (RR = 0.88, 95% CI 0.77, 0.99) were associated with in-health facility deliveries. In Guatemala, increased availability of medications and equipment at a distant facility was strongly associated with bypassing the closest facility in favor of a distant one for delivery (RR = 2.10, 95% CI 1.08, 4.07). Our study showed a strong correlation between well-equipped facilities and delivery attendance in poor areas of Mesoamerica. Indeed, women were more likely to travel to more distant facilities if the facilities were of higher level, which scored higher on our capacity score. Our findings call for improving the capacity of health facilities, quality of care and addressing cultural and accessibility barriers to increase institutional delivery among the poor population in Mesoamerica.

ObjectivesHaemorrhage 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.DesignPre-post study.Setting166 basic-level and comprehensive-level health facilities in Belize, Guatemala, Honduras, Mexico, Nicaragua and Panama.ParticipantsA random sample of medical records for uncomplicated full-term deliveries (n=2470) per International Classification of Diseases coding at baseline (July 2011 to August 2013) and at first-phase follow-up (January 2014 to October 2014).InterventionsA year of intervention implementation prior to first-phase follow-up data collection focused on improving access to oxytocin by strengthening supply chains, procurement, storage practices and pharmacy inventory monitoring, using a results-based financing model.Primary and secondary outcome measuresOxytocin availability (primary outcome) and administration (secondary outcome) for postpartum haemorrhage prevention.ResultsAvailability of oxytocin increased from 82.9% to 97.6%. Oxytocin administration increased from 83.6% to 88.4%. Significant improvements were seen for availability of oxytocin (adjusted OR (aOR)=8.41, 95% CI 1.50 to 47.30). Administration of oxytocin was found to be significantly higher in Honduras (aOR=2.96; 95% CI 1.00 to 8.76) in reference to Guatemala at follow-up.ConclusionAfter interventions to increase health facility supplies, the study showed a significant improvement in availability but not administration of oxytocin in poor communities within Mesoamerica. Efforts are needed to improve the use of oxytocin.

El presente estudio hace una revision de los factores asociados a la cantidad y oportunidad de las consultas de atencion prenatal (AP) para mujeres pobres de Guatemala, Honduras, Mexico, Nicaragua, Panama y El Salvador. Entrevistamos a 8,366 mujeres respecto a la AP que recibieron considerando su parto mas reciente en los ultimos dos anos. Llevamos a cabo regresiones logisticas para a analizar caracteristicas demograficas, de hogares y de salud asociadas a la asistencia a por lo menos una consulta de AP por personal calificado, cuatro consultas con personal calificado y una consulta con personal calificado durante el primer trimestre del embarazo. Encontramos que, en los paises del estudio, un 78% de las mujeres asistio a por lo menos una consulta de AP por personal calificado, mientras que un 62% concurrio por lo menos a cuatro consultas por personal calificado y un 56% asistio a una consulta con profesionales de salud durante el primer trimestre del embarazo. El pais que registro la mayor proporcion de mujeres que asistieron a consultas de AP por personal calificado fue Nicaragua (81%), mientras que Guatemala y Panama tuvieron la proporcion mas baja (18% y 38% respectivamente). En multiples paises, las mujeres solteras, con menor nivel educativo, adolescentes, indigenas, que no deseaban concebir y carecian de exposicion a los medios masivos de comunicacion presentaron menos probabilidades de cumplir con las directrices internacionales sobre AP. A pesar de las vastas reformas a las politicas y de numerosas iniciativas orientadas a los pobres, muchas mujeres de las areas mas pobres de Mesoamerica siguen sin recibir la atencion prenatal adecuada.

Care practices and risk factors for diarrhea among impoverished communities across Mesoamerica are unknown. Using Salud Mesoamerica 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. We compared diarrhea prevalence and treatment modalities using χ(2) tests and used multivariable Poisson regression models to calculate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for potential correlates of diarrhea. The 2-week point prevalence of diarrhea was 13% overall, with significant differences between countries (P < 0.05). Approximately one-third of diarrheal children were given oral rehydration solution and less than 3% were given zinc. Approximately 18% were given much less to drink than usual or nothing to drink at all. Antimotility medication was given to 17% of diarrheal children, while antibiotics were inappropriately given to 36%. In a multivariable regression model, compared with children 0-5 months, those 6-23 months had a 49% increased risk for diarrhea (aRR = 1.49, 95% CI = 1.15, 1.95). Our results call for programs to examine and remedy low adherence to evidence-based treatment guidelines.

Research on network-level influences on HIV risk behaviors among young men in sub-Saharan Africa is severely lacking. One significant gap in the literature that may provide direction for future research with this population is understanding the degree to which various HIV risk behaviors and normative beliefs cluster within men’s social networks. Such research may help us understand which HIV-related norms and behaviors have the greatest potential to be changed through social influence. Additionally, few network-based studies have described the structure of social networks of young men in sub-Saharan Africa. Understanding the structure of men’s peer networks may motivate future research examining the ways in which network structures shape the spread of information, adoption of norms, and diffusion of behaviors. We contribute to filling these gaps by using social network analysis and multilevel modeling to describe a unique dataset of mostly young men (n= 1,249 men and 242 women) nested within 59 urban social networks in Dar es Salaam, Tanzania. We examine the means, ranges, and clustering of men’s HIV-related normative beliefs and behaviors. Networks in this urban setting varied substantially in both composition and structure and a large proportion of men engaged in risky behaviors including inconsistent condom use, sexual partner concurrency, and intimate partner violence perpetration. We found significant clustering of normative beliefs and risk behaviors within these men’s social networks. Specifically, network membership explained between 5.78 and 7.17% of variance in men’s normative beliefs and between 1.93 and 15.79% of variance in risk behaviors. Our results suggest that social networks are important socialization sites for young men and may influence the adoption of norms and behaviors. We conclude by calling for more research on men’s social networks in Sub-Saharan Africa and map out several areas of future inquiry.

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 Mesoamerica Initiative to analyze data from 10,895 indigenous and non-indigenous women in Guatemala and Mexico (Chiapas State) and indigenous women in Panama. We created multivariable Poisson regression models for indigenous (Guatemala, Mexico, Panama) and non-indigenous (Guatemala, Mexico) women to identify correlates of institutional delivery and satisfaction. Compared to their non-indigenous peers, indigenous women were substantially less likely to have an institutional delivery (15.2% vs. 41.5% in Guatemala (P

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. We also assessed the predictors of breastfeeding behaviors to identify factors amenable to policy interventions. METHODS: We analyzed data from 12529 children in Guatemala Honduras Mexico (Chiapas State) Nicaragua Panama and El Salvador using baseline survey data from the Salud Mesoamerica 2015 Initiative. We created multivariable Poisson regression models with robust variance estimates to calculate adjusted risk ratios (aRRs) and 95% CIs for breastfeeding outcomes and to control for sociodemographic and healthcare-related factors. RESULTS: Approximately 97% of women in all countries breastfed their child at least once and 65.1% (Nicaragua) to 79.0% (Panama) continued to do so between 6 mo and 2 y of age. Breastfeeding in the first hour of life varied by country (P < 0.001) with the highest proportion reported in Panama (89.8%) and the lowest in El Salvador (65.6%). Exclusive breastfeeding also varied by country (P = 0.037) ranging from 44.5% in Panama to 76.8% in Guatemala. For every 20% increase in the proportion of peers who exclusively breastfed there was an 11% (aRR: 1.11 95% CI: 1.04 1.18) increase in the likelihood of exclusive breastfeeding. CONCLUSION: Our study revealed significant variation in the prevalence of breastfeeding practices by poor women across countries surveyed by the Salud Mesoamerica 2015 initiative. Future interventions to promote exclusive breastfeeding should consider ways to leverage the role of the community in supporting individual women. (c) 2015 American Society for Nutrition.

Background Health has improved markedly in Mesoamerica, the region consisting of southern Mexico and Central America, over the past decade. Despite this progress, there remain substantial inequalities in health outcomes, access, and quality of medical care between and within countries. Poor, indigenous, and rural populations have considerably worse health indicators than national or regional averages. In an effort to address these health inequalities, the Salud Mesoamérica 2015 Initiative (SM2015), a results-based financing initiative, was established. Methods For each of the eight participating countries, health targets were set to measure the progress of improvements in maternal and child health produced by the Initiative. To establish a baseline, we conducted censuses of 90,000 households, completed 20,225 household interviews, and surveyed 479 health facilities in the poorest areas of Mesoamerica. Pairing health facility and household surveys allows us to link barriers to care and health outcomes with health system infrastructure components and quality of health services. Results Indicators varied significantly within and between countries. Anemia was most prevalent in Panama and least prevalent in Honduras. Anemia varied by age, with the highest levels observed among children aged 0 to 11 months in all settings. Belize had the highest proportion of institutional deliveries (99%), while Guatemala had the lowest (24%). The proportion of women with four antenatal care visits with a skilled attendant was highest in El Salvador (90%) and the lowest in Guatemala (20%). Availability of contraceptives also varied. The availability of condoms ranged from 83% in Nicaragua to 97% in Honduras. Oral contraceptive pills and injectable contraceptives were available in just 75% of facilities in Panama. IUDs were observed in only 21.5% of facilities surveyed in El Salvador. Conclusions These data provide a baseline of much-needed information for evidence-based action on health throughout Mesoamerica. Our baseline estimates reflect large disparities in health indicators within and between countries and will facilitate the evaluation of interventions and investments deployed in the region over the next three to five years. SM2015’s innovative monitoring and evaluation framework will allow health officials with limited resources to identify and target areas of greatest need. Electronic supplementary material The online version of this article (doi:10.1186/s12963-015-0034-4) contains supplementary material, which is available to authorized users.

Background Poor women in the developing world have a heightened need for antenatal care (ANC) but are often the least likely to attend it. This study examines factors associated with the number and timing of ANC visits for poor women in Guatemala, Honduras, Mexico, Nicaragua, Panama, and El Salvador. Methods We surveyed 8366 women regarding the ANC they attended for their most recent birth in the past two years. We conducted logistic regressions to examine demographic, household, and health characteristics associated with attending at least one skilled ANC visit, four skilled visits, and a skilled visit in the first trimester. Results Across countries, 78 % of women attended at least one skilled ANC visit, 62 % attended at least four skilled visits, and 56 % attended a skilled visit in the first trimester. The proportion of women attending four skilled visits was highest in Nicaragua (81 %) and lowest in Guatemala (18 %) and Panama (38 %). In multiple countries, women who were unmarried, less-educated, adolescent, indigenous, had not wanted to conceive, and lacked media exposure were less likely to meet international ANC guidelines. In countries with health insurance programs, coverage was associated with attending skilled ANC, but not the timeliness. Conclusions Despite significant policy reforms and initiatives targeting the poor, many women living in the poorest regions of Mesoamérica are not meeting ANC guidelines. Both supply and demand interventions are needed to prioritize vulnerable groups, reduce unplanned pregnancies, and reach populations not exposed to common forms of media. Top performing municipalities can inform effective practices across the region.

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. We used multivariable logistic regression to measure the association between delivering a child in a health facility and select household and maternal characteristics, including education and measures of wealth. Results Health indicators varied greatly between geographic segments. Controlling for other demographic characteristics, women with at least secondary education were more likely to have an in-facility delivery compared to women who had not attended school (OR: 3.20, 95 % confidence interval [CI]: 2.56-3.99, respectively). Similarly, women from households with the highest expenditure were more likely to deliver in a health facility compared to those from the lowest expenditure households (OR 3.06, 95 % CI: 2.43-3.85). Household assets did not impact these associations. Moreover, we found that commonly-used definitions of poverty do not align with the disparities in health outcomes observed in these communities. Conclusions Although poverty measured by expenditure or wealth is associated with health disparities or health outcomes, a composite indicator of health poverty based on coverage is more likely to focus attention on health problems and solutions. Our findings call for the public health community to define poverty by health coverage measures rather than income or wealth. Such a health-poverty metric is more likely to generate attention and mobilize targeted action by the health communities than our current definition of poverty.