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- Title
Chemoprophylaxis under sporozoites-lumefantrine (CPS-LMF) immunization induce protective immune responses against Plasmodium yoelii sporozoites infection in mice.
- Authors
Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Hamadou, Walid Sabri; Goyal, Manish; Ashraf, Syed Amir; Jahan, Sadaf; Jamal, Arshad; Sharma, Pankaj; Sachidanandan, Manojkumar; Badraoui, Riadh; Adnan, Mohd
- Abstract
Malaria represents one of the major life-threatening diseases that poses a huge socio-economic impact, worldwide. Chemoprophylaxis vaccination using a relatively low number of wild-type infectious sporozoites represents an attractive and effective vaccine strategy against malaria. However, the role of immune responses to pre-erythrocytic versus blood-stage parasites in protection against different antimalarial drugs remains unclear. Here, in the present study, we explored the immune responses against the repetitive inoculation of live Plasmodium yoelii (P. yoelii) sporozoites in an experimental Swiss mouse model under antimalarial drug lumefantrine chemoprophylaxis (CPS-LMF). We monitored the liver stage parasitic load, pro/anti-inflammatory cytokines expression, and erythrocytic stage patency, following repetitive cycles of sporozoites inoculations. It was found that repetitive sporozoites inoculation under CPS-LMF results in delayed blood-stage infection during the fourth sporozoites challenge, while sterile protection was produced in mice following the fifth cycle of sporozoites challenge. Intriguingly, we observed a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and iNOS response and down-regulation of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) in the liver HMNC (hepatic mononuclear cells) and spleen cells after 4th and 5th cycle of sporozoites challenge in the CPS-LMF mice. Meanwhile, we also noticed that the liver stage parasites load under CPS-LMF immunization has gradually reduced after 2nd, 3rd, 4th and 5th sporozoites challenge. Overall, our study suggests that chemoprophylaxis vaccination under LMF drug cover develops strong immune responses and confer superior long-lasting protection against P. yoelii sporozoites. Furthermore, this vaccination strategy can be used to study the protective and stage-specific immunity against new protective antigens.
- Subjects
PLASMODIUM yoelii; SPOROZOITES; VACCINE effectiveness; IMMUNE response; CHEMOPREVENTION; MALARIA; PLASMODIUM; PARASITES
- Publication
3 Biotech, 2021, Vol 11, Issue 11, p1
- ISSN
2190-572X
- Publication type
Article
- DOI
10.1007/s13205-021-03022-0