Persistent Plasmodium falciparum infections enhance transmission-reducing immunity development.

Subclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks. Of the 100 participants, only 11 were never infected, whilst 16 had persistent infections detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and one participant had microscopic parasites at all visits. Over 70% of the participants were infected three or more times, and submicroscopic gametocyte prevalence was high, ≥ 48% of the parasite carriers. Naturally induced responses against recombinant Pfs48/45.6C, Pfs230proC, and EBA175RIII-V antigens were not associated with either infection status or gametocyte carriage, but the antigen-specific IgG titers inversely correlated with parasite and gametocyte densities consistent with partial immunity. Longitudinal analysis of gametocyte diversity indicated at least four distinct clones circulated throughout the study period. The high prevalence of children infected with distinct gametocyte clones coupled with marked variation in infection status at the individual level suggests ongoing transmission and should be targeted in malaria control programs.

Development and application of therapeutic antibodies against COVID-19.

The pandemic of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2) continues to be a global health crisis. Fundamental studies at genome, transcriptome, proteome, and interactome levels have revealed many viral and host targets for therapeutic interventions. Hundreds of antibodies for treating COVID-19 have been developed at preclinical and clinical stages in the format of polyclonal antibodies, monoclonal antibodies, and cocktail antibodies. Four products, i.e., convalescent plasma, bamlanivimab, REGN-Cov2, and the cocktail of bamlanivimab and etesevimab have been authorized by the U.S. Food and Drug Administration (FDA) for emergency use. Hundreds of relevant clinical trials are ongoing worldwide. Therapeutic antibody therapies have been a very active and crucial part of COVID-19 treatment. In this review, we focus on the progress of therapeutic COVID-19 antibody development and application, discuss corresponding problems and challenges, suggesting new strategies and solutions.

Stage-specific Plasmodium falciparum immune responses in afebrile adults and children living in the Greater Accra Region of Ghana.

BACKGROUND: Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana. METHODS: Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at - 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA. RESULTS: Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom. CONCLUSION: The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gametocyte prevalence decreased in the rainy season relative to the dry season.

Diversity and immune responses against Plasmodium falciparum gametocytes in non-febrile school children living in Southern Ghana.

BACKGROUND: Natural exposure to gametocytes can result in the development of immunity against the gametocyte by the host as well as genetic diversity in the gametocyte. This study evaluated the quantity and quality of natural immune responses against a gametocyte antigen, Pfs230 as well as the prevalence and diversity of gametocytes circulating in children living in two communities in southern Ghana. METHODS: Whole blood (2.5 ml) was collected from 137 non-febrile school children aged between 6 and 12 years old quarterly for a 6-month period. A drop of blood was used to prepare thick and thin blood films for parasite prevalence and density estimation. Subsequently, stored plasma samples were used in ELISAs assays to measure antibody responses and avidity against Pfs230. RNA was extraction from Trizol preserved packed cells and subsequently converted to complementary DNA (cDNA) which was used for reverse transcriptase PCR (RT-PCR) to determine gametocytes prevalence and diversity. RESULTS: Gametocyte carriage in the peak season (July) determined by Pfg377 RT-PCR was 49.2% in Obom and 22.2% in Abura, and was higher than that determined by microscopy. Gametocyte diversity was low and predominated by the same allele at both sites. The relative avidity index for antibodies measured in Abura was higher than that recorded in Obom at all time points although Pfs230 IgG concentrations were significantly high (P < 0.0001) in Obom than in Abura at all time points. The IgG responses in Obom were significantly higher than that in Abura during the peak season. CONCLUSION: Naturally induced antibody responses against Pfs230 in children living in both high perennial and low seasonal malaria transmission settings reduced significantly in moving from the peak to the off-peak season. The relative avidity of antibodies against Pfs230 in Abura was significantly higher than those measured in Obom, despite having lower IgG levels. Very limited diversity was identified in the gametocytes circulating in both Obom and Abura.

Assessment of the quality and quantity of naturally induced antibody responses to EBA175RIII-V in Ghanaian children living in two communities with varying malaria transmission patterns.

BACKGROUND: Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII-VLl in asymptomatic children living in two communities with varying malaria transmission patterns. METHODS: An asexual stage Plasmodium falciparum antigen, EBA175RIII-VLl was expressed in Lactococcus lactis, purified and used in indirect ELISA to measure total and cytophilic IgG concentrations and avidities in children aged between 6 and 12 years. The children were selected from Obom and Abura, communities with perennial and seasonal malaria transmission, respectively. Venous blood samples were collected in July and October 2015 and again in January 2016. The multiplicity of infection and the genetic diversity of EBA175RIII circulating in both sites were also assessed using polymerase chain reaction. RESULTS: Asymptomatic parasite carriage in the children from Obom decreased from July (peak season), through October and January, however parasite carriage in children from Abura was bimodal, with the lowest prevalence estimated in October. Antibody concentrations over the course of the study remained stable within each study site however, children living in Obom had significantly higher EBA175RIII-VLl antibody concentrations than children living in Abura (P < 0.05, Mann-Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII-VLl IgG antibodies were similar within and between the sites. CONCLUSION: Naturally acquired IgG concentrations but not relative antibody avidities to EBA175RIII-V were significantly higher in Obom where malaria transmission is perennial than in Abura, where malaria transmission is seasonal.