bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.11.03.514987

Mosquito bites and stages specific antibody responses against Plasmodium falciparum in southern Ghana

Abstract

BackgroundThe human host elicits specific immune responses after exposure to various life stages of the malaria parasite as well as components of mosquito saliva injected into the host during a mosquito bite. This study describes differences in IgG responses against antigens derived from the sporozoite (PfCSP), asexual stage parasite (PfEBA175) and the gametocyte (Pfs230) in addition to an Anopheles gambiae salivary gland antigen (gSG6-P1) in two communities in Ghana with similar blood stage malaria parasite prevalence. MethodologyThis study used archived plasma samples collected from an earlier cross-sectional study that enrolled volunteers aged from 6 months to 70 years from Simiw, peri-urban community (N=347) and Obom, rural community (N=291). An archived thick and thin blood smear for microscopy was used for the estimation of Plasmodium parasite density and species and DNA extraction from blood spots and P. falciparum confirmation was performed using PCR. This study used the stored plasma samples to determine IgG antibody levels to Plasmodium falciparum and Anopheles salivary antigens using indirect ELISA. ResultsIndividuals from Simiw had significantly higher levels of IgG against mosquito gSG6-P1 (median (95%CI)) (2.590 (2.452-2.783) ng/mL) compared to those from Obom (2.119 (1.957-2.345) ng/mL), p<0.0001. Both IgG responses against Pfs230proC (p=0.0006), and PfCSP (p=0.002) were significantly lower in volunteers from Simiw compared to the participants from Obom. The seroprevalence of PfEBA-175.5R (p=0.8613), gSG6-P1 (p=0.0704), PfCSP (p=0.7798) IgG were all similar in Obom and Simiw. However, Pfs230 seroprevalence was significantly higher at Obom compared to Simiw (p=0.0006). Spearman correlation analysis showed no significant association between IgG responses against gSG6-P1, PfCSP, Pfs230proC and PfEBA-175.5R and parasite density at both Obom and Simiw (p>0.05). ConclusionIn conclusion, malaria transmission dynamics is highly complex. The similar malaria transmission intensity identified in the two communities resulted from a different combination of vector, environmental and host factors. With one community likely having a higher prevalence of uninfected mosquitoes and the other a larger reservoir of gametocyte carriers.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kwapong, S. S., Asare, K. K., Kusi, K. A., Pappoe, F., Ndam, N., Tahar, R., Poinsignon, A., Amoah, L. E.. 2022-11-04. Mosquito bites and stages specific antibody responses against Plasmodium falciparum in southern Ghana. https://doi.org/10.1101/2022.11.03.514987

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Ksp37 is a rapidly mobilized NK cell secretory protein that engages FGF2

A key feature of natural killer (NK) cells is their preloaded arsenal of effector molecules, allowing them to rapidly respond upon activation. In this study, we characterized a previously unexplored secretory protein, termed killer-specific secretory protein of 37 kDa (Ksp37), which is highly abundant in differentiated CD56dim NK cells. Ksp37 is rapidly secreted in a dose-dependent and JAK-1 dependent manner upon low levels of cytokine stimulation, making it a sensitive readout for NK cell activation. Following secretion, intracellular levels were rapidly replenished, preserving responsiveness to subsequent cytokine stimulation. We found that Ksp37 is stored in polarized intracellular compartments distinct from those containing canonical cytotoxic effector molecules, including granzyme B and perforin, which require stronger stimulation for release. Lastly, we identified Ksp37 as a novel binding partner of fibroblast growth factor 2 (FGF2). This opens new avenues of exploration for the role of NK cells in remodeling their extracellular environment by modulating the FGF2-FGFR1 axis, which plays a key role in tumor growth, angiogenesis and tissue repair.

immunology↗

ACE-engineered human iPSC-derived neutrophils enhance host defense against multidrug-resistant bacterial infections

Severe neutropenia predisposes patients to life-threatening infections, while donor-dependent granulocyte transfusions are limited by availability and variable cell quality. Here, we engineered human induced pluripotent stem cells (iPSCs) to constitutively or inducibly express angiotensin-converting enzyme (ACE) and differentiated them into functional ACE-engineered neutrophils (ACE-iNeu). ACE expression enhanced granulocytic maturation, reactive oxygen species generation, inflammatory cytokine production, and antimicrobial signaling. ACE-iNeu exhibited enhanced bactericidal activity against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. Following adoptive transfer into neutropenic mice, ACE-iNeu significantly reduced circulating and tissue bacterial burdens. Integrated metabolomic and transcriptomic analyses revealed ACE-associated alterations in adenine nucleotide abundance and developmental and inflammatory pathways. Together, these findings establish ACE engineering as a strategy to enhance the production and antimicrobial function of human iPSC-derived neutrophils and support further preclinical development of engineered granulocyte therapies for severe drug-resistant infections.

immunology↗

Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.

An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.

immunology↗