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Biology subjects

Esen, M.

Publications and source records attributed to Esen, M..

4 recordsLinked to original sources

Microfilaremic loiasis is associated with T cell hyporesponsiveness against SARS CoV-2

BackgroundLoiasis is a chronic filarial infection endemic to Central and West Africa. Although long considered benign, increasing evidence links loiasis to substantial morbidity and mortality. The infection is associated with immune modulation, including Th2-skewed responses and elevated regulatory cytokines. Clinically, loiasis is classified as microfilaremic (presence of circulating microfilariae) or amicrofilaremic ("occult") disease, the latter defined by a history of eyeworm migration without detectable microfilaremia. This study investigated how chronic L. loa infection influences antibody and T cell responses to SARS-CoV-2 following natural infection. MethodsBetween 2022 and 2024 this cross-sectional study was done in Lambarene and surrounding rural areas of Gabon. Study procedures included diagnostics for loiasis and immunological assays. Microfilaremia was confirmed by stained blood smear microscopy, and occult disease was identified using the Rapid Assessment Procedure for Loiasis. SARS-CoV-2-specific IgG responses to spike and nucleocapsid proteins were measured by ELISA, and IFN-{gamma} responses to spike antigen were assessed using an interferon-gamma release assay. ResultsOverall, 192 participants were categorized as microfilaremic (n=43), occult loiasis (n=59), or without evidence of active loiasis (n=90). IFN-{gamma} responses were reduced in microfilaremic individuals compared with other participants (p= 0.031), whereas IgG responses did not differ. Subsequent analysis across the three groups confirmed that IFN-{gamma} responses were lower in microfilaremic compared with occult participants (p= 0.012). ConclusionThese findings suggest that microfilaremic loiasis may impair proinflammatory T cell responses to viral antigens, highlighting the need for further research into the broader immunological effects of Loa loa infection in endemic populations. Authors summaryLoiasis is a parasitic infection caused by the worm Loa loa and is common in parts of Central and West Africa. Although long considered relatively benign, growing evidence indicates that loiasis is associated with substantial morbidity. The immunological consequences of chronic Loa loa infection remain poorly understood. A small number of studies suggest that Loa loa may influence immune regulation, but its broader impact on antiviral immunity is largely unknown. The COVID-19 pandemic provided a unique opportunity to examine immune responses to a newly emerging virus in a population where loiasis is endemic. We therefore investigated how different forms of Loa loa infection influence immune responses after natural SARS-CoV-2 infection. We compared individuals with circulating microfilariae in their blood (microfilaremic), individuals with occult loiasis (history of eye worm), and individuals without signs of active infection. We found that microfilaremic individuals had weaker virus-specific IFN-{gamma} T cell responses, while antibody levels were similar across groups. These findings suggest that active loiasis may dampen certain antiviral immune functions. Understanding the underlying mechanisms is important, as such immune modulation could affect responses to vaccines and other infectious diseases in endemic regions.

immunology↗

Flagellin in the human gut microbiome is a diet-adjustable adjuvant for vaccination

The intestinal microbiota is thought to modulate immune responsiveness to vaccines. Human studies on this topic, however, have yielded inconsistent results1,2. We hypothesized that the microbiome would influence innate immune responses, and thus vaccine reactogenicity, more directly than vaccine immunogenicity. To test this, we established the {micro}HEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 171 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. Increased temperature after vaccination ({Delta}T) was associated with habitual diet and with baseline metabolic and immune markers. The microbiomes of {Delta}T-high ({Delta}Thi) participants were characterized by high expression of flagellin and an overabundance of the flagellated bacterium Waltera. Fecal samples from {Delta}Thi participants induced more inflammation in human cells and stronger post-vaccine temperature responses in mice compared to {Delta}Tlo samples, suggesting a causal role for the microbiome. Moreover, Waltera flagellin replicated the inflammatory phenotypes in vitro and was modulable via a dietary additive. Overall, these data suggest that flagellin from the gut microbiome stimulates innate immunity and vaccine reactogenicity, and that this axis can be manipulated via diet. These findings have implications for improving human vaccine tolerance and immunogenicity.

microbiology↗

Codiversification of gut microbiota with humans

Some gut microbes have cospeciated with hominids, but whether they further codiversified with human populations is unclear. Here, we identify predominant gut microbial species sharing a parallel evolutionary history with human populations. Patterns of strain transfer between populations are generally consistent with an African origin, and suggest long-term vertical transmission over thousands of generations. We show the same strains also faithfully transmit between mothers and their children. Consistent with the development of intimate symbiosis, species with strongest patterns of codiversification have the smallest genomes. This study reveals long-term fidelity of gut microbiota with human populations through transmission among individuals living in close proximity. Dominance of specific strains in different populations is based in part on vertical transmission and they may provide population-specific health benefits. One-sentence summaryIdentification of gut microbes that codiversified with human populations.

evolutionary biology↗

Mapping of safe and early chemo-attenuated live Plasmodium falciparum immunization identifies immune signature of vaccine efficacy

Potent protection against malaria can be induced by attenuated live-immunization with Plasmodium falciparum (Pf) sporozoites (SPZ). However, a better understanding of the critical processes involved in the establishment of protective immunity is needed. We explored the safety and vaccine efficacy of early chemo-attenuation of PfSPZ under atovaquone-proguanil (AP). AP caused early arrest of P. berghei liver stages. Despite the absence of replication, robust protection in mice correlated with parasite-specific effector-memory CD8+ T-cell responses. In a phase I clinical trial a single dose of AP prevented Pf infections in the liver of adult, human subjects who received three doses of 5.12x104 or 1.5x105 PfSPZ by direct venous inoculation combined with oral AP. However, only 2 of 8 (25%) and 2 of 10 (20%), respectively, were protected against controlled human malaria infection (CHMI) 10 weeks after the last vaccine dose, despite levels of IgG antibodies to the Pf circumsporozoite protein (PfCSP) comparable to those achieved in fully protected volunteers after immunization with 5.12x104 PfSPZ with chloroquine chemoprophylaxis active only against subsequent blood stages. We identify lower IgG recognition of the secreted liver stage-specific antigens LISP2 and LSA1 and the multi-stage antigen MSP5 as immune signatures of inferior vaccine efficacy compared to PfSPZ with chloroquine chemoprophylaxis. In conclusion, we show that immune signatures of liver stage antigens, but neither an established rodent malaria model nor concentrations of antibodies against the major surface protein of sporozoites, permit prediction of vaccine efficacy. Thus, this study provides a clear rationale for the development of live sporozoite vaccination protocols that boost exposure to Pf liver stage antigens. Significance StatementOur research demonstrates that attenuation of liver infection of high doses of Plasmodium falciparum sporozoites by concomitant single-dose administration of atovaquone-proguanil is safe in humans. However, vaccine efficacy was modest when compared to an identical protocol using chloroquine that acts only on the subsequent blood infection. Immune signatures of secreted P. falciparum liver stage antigens, but neither an established rodent malaria model nor concentrations of sporozoite antibodies, permit prediction of vaccine efficacy.

immunology↗