Search

Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. However, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. It implies that there is still a need to explore new vaccine strategies. Lentiviral vectors are very potent at inducing strong immunological memory. However their integrative status challenges their safety profile. Eliminating the integration step obviates the risk of insertional oncogenesis. Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV) hold promise as mass pediatric vaccine by meeting high safety standards. In this study, we have assessed the protective efficacy of NILV against malaria in a robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium yoelii Circumsporozoite Protein (Py CSP) and challenged with sporozoites one month later. In two independent protective efficacy studies, 50% (37.5-62.5) of the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when compared to naive mice). The remaining mice with detectable parasitized red blood cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection was long-lasting with 42.8% sterile protection six months after the last immunization (p = 0.0042). Post-challenge CD8+ T cells to CSP, in contrast to anti-CSP antibodies, were associated with protection (r = -0.6615 and p = 0.0004 between the frequency of IFN-g secreting specific T cells in spleen and parasitemia). However, while NILV and RAS immunizations elicited comparable immunity to CSP, only RAS conferred 100% of sterile protection. Given that a better protection can be anticipated from a multi-antigen vaccine and an optimized vector design, NILV appear as a promising malaria vaccine.

Background: The relationship between malaria and obesity are largely unknown. This is partly due to the fact that malaria occurs mainly in tropical areas where, until recently, obesity was not prevalent. It now appears, however, that obesity is emerging as a problem in developing countries. To investigate the possible role of obesity on the host-parasite response to malarial infection, this study applied a murine model, which uses the existence of genetically well characterized obese mice. Methods: The receptivity of obese homozygous ob/ob mice was compared to the receptivity of control heterozygous ob/+ lean mice after a single injection of Plasmodium berghei ANKA sporozoites. Both parasitaemia and mortality in response to infection were recorded. Results: The control mice developed the expected rapid neurological syndromes associated with the ANKA strain, leading to death after six days, in absence of high parasitaemia. The obese mice, on the other hand, did not develop cerebral malaria and responded with increasing parasitaemia, which produced severe anemia leading to death 18-25 days after injection. Conclusion: The observed major differences in outward symptoms for malarial infection in obese versus control mice indicate a link between obesity and resistance to the infection which could be addressed by malariologists studying human malaria. [ABSTRACT FROM AUTHOR]