Protective efficacy and correlates of immunity of immunodominant recombinant Babesia microti antigens.
Scott MeredithVictoria MajamHong ZhengNitin VermaAnkit PuriAdovi AkueMark KuKurugaMiranda OakleySanjai KumarPublished in: Infection and immunity (2023)
Babesia microti, an intraerythrocytic apicomplexan parasite, is the primary causative agent of human babesiosis and an emerging threat to public health in the United States and elsewhere. An effective vaccine against B. microti would reduce disease severity in acute babesiosis patients and shorten the parasitemic period in asymptomatic individuals, thereby minimizing the risk of transfusion-transmitted babesiosis. Here we report on immunogenicity, protective efficacy, and correlates of immunity following immunization with four immunodominant recombinantly produced B. microti antigens-Serine Reactive Antigen 1 (SERA1), Maltese Cross Form Related Protein 1 (MCFRP1), Piroplasm β-Strand Domain 1 (PiβS1), and Babesia microti Alpha Helical Cell Surface Protein 1 (BAHCS1)-delivered subcutaneously in Montanide ISA 51/CpG adjuvant in three doses to BALB/c mice. Following B. microti parasite challenge, BAHCS1 led to the highest reduction in peak parasitemia (67.8%), followed by SERA1 (44.8%) and MCFRP1 (41.9%); PiβS1 (27.6%) had minimal protective effect. All four B. microti antigens induced high ELISA total IgG and each isotype; however, antibody levels did not directly correlate with anti-parasitic activity in mice. Increased prechallenge levels of some cell populations including follicular helper T cells (T FH ) and memory B cells, along with a set of six cytokines [IL-1α, IL-2, IL-3, IL-6, IL-12(p40), and G-CSF] that belong to both innate and adaptive immune responses, were generally associated with protective immunity. Our results indicate that mechanisms driving recombinant B. microti antigen-induced immunity are complex and multifactorial. We think that BAHCS1 warrants further evaluation in preclinical studies.
Keyphrases
- immune response
- public health
- dendritic cells
- end stage renal disease
- endothelial cells
- high glucose
- cell surface
- drug induced
- diabetic rats
- chronic kidney disease
- adipose tissue
- early stage
- type diabetes
- stem cells
- newly diagnosed
- high fat diet induced
- single cell
- bone marrow
- working memory
- intensive care unit
- small molecule
- patient reported outcomes
- metabolic syndrome
- amino acid
- cell therapy
- case control
- induced pluripotent stem cells
- life cycle
- light emitting