Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria.

Acute gastroenteritis (AGE) has one of the highest rates of morbidity and mortality among children under five years old worldwide. It is estimated that 1.7 billion cases of childhood diarrheal diseases occur annually, leading to up to 443,832 deaths. Approximately 90% of these cases are viral, with human norovirus being the main cause in countries that have implemented rotavirus vaccines. The objective of this study was to describe the prevalence and genetic diversity of norovirus in child outpatients and inpatients under five years old at the Regional Hospital of Antofagasta. From 1 January to 31 October 2019, a total of 121 stool samples were collected to detect the presence of norovirus GI and GII using Taqman™-based real-time RT-PCR. Norovirus RNA was detected in 50 (41.3%) samples, of which 96% were typed as GII.4 Sydney (42% GII.4 Sydney[P16] and 54% GII.4 Sydney[P4 New Orleans]). Furthermore, most (92%) of the positive specimens were from children under two years of age and a majority were detected in April (38%) and May (20%). Our findings highlight the high burden of norovirus in hospitalized children with AGE and the importance of molecular strain surveillance to support vaccine development.

Although a lack of diversity in genetic studies is an acknowledged obstacle for personalized medicine and precision public health, Latin American populations remain particularly understudied despite their heterogeneity and mixed ancestry. This gap extends to COVID-19 despite its variability in susceptibility and clinical course, where ethnic background appears to influence disease severity, with non-Europeans facing higher hospitalization rates. In addition, access to high-quality samples and data is a critical issue for personalized and precision medicine, and it has become clear that the solution lies in biobanks. The creation of the Chilean COVID-19 Biorepository reported here addresses these gaps, representing the first nationwide multicentric Chilean initiative. It operates under rigorous biobanking standards and serves as one of South America’s largest COVID cohorts. A centralized harmonization strategy was chosen and included unified standard operating procedures, a sampling coding system, and biobanking staff training. Adults with confirmed SARS-CoV-2 infection provided broad informed consent. Samples were collected to preserve blood, plasma, buffy coat, and DNA. Quality controls included adherence to the standard preanalytical code, incident reporting, and DNA concentration and absorbance ratio 260/280 assessments. Detailed sociodemographic, health, medication, and preexisting condition data were gathered. In five months, 2262 participants were enrolled, pseudonymized, and sorted by disease severity. The average Amerindian ancestry considering all participant was 44.0% [SD 15.5%], and this value increased to 61.2% [SD 19.5%] among those who self-identified as Native South Americans. Notably, 279 participants self-identified with one of 12 ethnic groups. High compliance (>90%) in all assessed quality controls was achieved. Looking ahead, our team founded the COVID-19 Genomics Network (C19-GenoNet) focused on identifying genetic factors influencing SARS-CoV-2 outcomes. In conclusion, this bottom-up collaborative effort aims to promote the integration of Latin American populations into global genetic research and welcomes collaborations supporting this endeavor. Interested parties are invited to explore collaboration opportunities through our catalog, accessible online.

The Phospholipase D (PLD) toxin family, a major component of the Loxosceles spider venom, is a valuable biotechnological tool for developing antivenom treatment and diagnostic assays to overcome and prevent loxoscelism. However, there is limited knowledge about the antigenic structure of the PLD family or if sequence diversity correlates with antigenic variability. This study aimed to evaluate the possible antigenic diversity of PLDs sequences among different species of spiders of the Loxosceles genus through a predictive analysis of potential continuous and discontinuous antigenic epitopes of two phylogenetic interspecies clusters. Thus, L. laeta had higher amino acid sequence variation than other species, being classified into three phylogenetic clusters at the intra-specie level. Furthermore, multiple alignments of consensus PLD sequences from each Loxosceles species showed two different phylogenetic clusters at interspecies level depending on the amino acid conservation. For each cluster, at least nine continuous antigenic domains were identified, and depending on the phylogenetic cluster belonging to the Loxosceles species, the PLD continuous and discontinuous antigenic structure varies. Also, L. laeta PLDs vary significantly within the Loxosceles species and possess their own antigenic structure compared to other species with common continuous epitopes. Finally, the catalytic loop was identified as a common discontinuous epitope in the PLDs independently of the cluster or the class it belongs to. This antigenic diversity of PLD toxins could have implications for antibody recognition and should be considered in the design strategies for the development of serum treatments and diagnostic assays to detect Loxosceles venom.

Purpose: Molecular mechanisms underlying COVID-19 susceptibility and severity are still poorly understood. The presence of genetic risk factors associated with ethnic background has been suggested, highlighting non-European ancestry as a risk factor for hospitalization in the United States. However, the representation of non-European populations in genomic case-control and cohort studies remains insufficient, and Latin American populations have been significantly understudied. Addressing this gap, we established The Chilean COVID-19 Biorepository, a multicentric endeavor comprising high-quality biological samples and associated data collected throughout Chile under stringent biobanking standards that ensure high quality, reproducibility, and interoperability. Participants: The Chilean COVID-19 Biorepository was established by a network of nine nodes distributed in five macro-zones nationwide. The study enrolled adult participants living in Chile who had tested positive for SARS-CoV-2 infection and provided broad written informed consent. Blood samples were collected with EDTA and processed to store blood, plasma, buffy-coat, and DNA. Quality control measures, such as Standard Preanalytical Code (SPREC), incident reporting, DNA concentration, and absorbance ratio (260/280), were implemented to ensure the reliability and quality of the collected samples. Sociodemographic data, habits, clinical information, use of medications, and preexisting pathologies were registered. A weekly iterative workflow was implemented to ensure the quality and integrity of specimens and data. Findings to date: Between October 2020 and February 2021, 2262 participants were recruited, pseudonymized, and categorized by disease severity into six categories, from asymptomatic to lethal. Notably, the Biorepository exhibited high compliance rates (>90%) across all quality control assessed items, reflecting high adherence to biobanking standards. A noteworthy feature of this cohort is the self-identification of 279 participants (12.3%) into thirteen different ethnic groups. Amerindian ancestry from genome-wide genetic data was 44.0%[SD15.5%] and increased to 61.2%[SD19.5%] when considering participants who identified as Native South Americans. As a data-contributor partner of the COVID-19 Host Genetics Initiative, the Chilean COVID-19 Biorepository has contributed to the publication of a second updated genome-wide association study, further enhancing our knowledge of the role of host genetics in susceptibility and severity to SARS-CoV-2. Future plans: The Chilean COVID-19 Biorepository, under the leadership of Latin American researchers from a Latin American country, substantially adds to the integration of Latin American populations in the global collections landscape. Just as ocurred with the COVID-19 Host Genetics Initiative, we expect that this repository will attract global network collaborations for comparative studies on the effects of COVID-19 across diverse populations, including exploring potential genetic advantages or disadvantages in the context of SARS-CoV-2 infection. Researchers involved in establishing this biorepository are currently associated within a collaborative initiative known as COVID-19 Genomics Network (C19-GenoNet), aimed to accelerate the identification of genetic factors in both hosts and pathogens that influence the short and long-term outcomes of SARS-CoV-2 infection. The broad informed consent utilized enables longitudinal cohort follow-up, thereby allowing for investigating the long-term consequences of SARS-CoV-2 infection, particularly concerning long-COVID. Thus, participants of this cohort were re-contacted to assess the development of long-COVID through a survey-based approach. The re-contact and recruitment procedures yielded a high response rate (82.11%), demonstrating strong participant engagement. In this case as well, this cohort has been leveraged by collaboration with the COVID-19 Host Genetics Initiative for the forthcoming publication of a genome-wide association study on long-COVID. The concerted endeavors invested in this Chilean initiative have led to the establishment and consolidation of C19-GenoNet as both a research network and a biobanking network. A comprehensive catalog of the C19-GenoNet biobank network has been created and is accessible online at https://redcovid.uchile.cl/ . STRENGHT AND LIMITATIONS OF THIS STUDY: This study is one of the largest cohorts of COVID-19 patients with associated Biobank reported so far in Latin America. The study’s design and rigorous weekly monitoring ensured effective collection of high-quality simples and maximized the quality and completeness of data, with the ability to re-contact participants in case of problematic information. There were no control or reliable information about the time between the infection and the sampling, which may hamper the comparison of some parameters among cases due to transcriptional dynamics after SARS-CoV-2 infection. The study is based on a self-reported survey, which may represent a bias when analyzing specific clinical phenotypes.