Association between anti‐Pfs48/45 reactivity and <i>P. falciparum</i> transmission‐blocking activity in sera from Cameroon

Roeffen, Will; Mulder, Bert; Teelen, Karina; Bolmer, M.; Eling, W.M.C.; Targett, G. A. T.; Beckers, Pascal; Sauerwein, Robert W.

doi:10.1046/j.1365-3024.1996.d01-54.x

Cited by 77 publications

(59 citation statements)

References 18 publications

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“…These antigens have a role in the fertilization or sporogonic development of malaria parasites in mosquitoes (43,44). A proportion of gametocytes die in the human host without being passed on to a mosquito, thereby exposing sexual stage antigens to the human immune system.…”

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confidence: 99%

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

et al. 2011

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Acquisition of immunity to Plasmodium falciparum sexual stages is a key determinant for reducing humanmosquito transmission by preventing the fertilization and the development of the parasite in the mosquito midgut. Naturally acquired immunity against sexual stages may therefore form the basis for the development of transmission-blocking vaccines, but studies conducted to date offer little in the way of consistent findings. Here, we describe the acquisition of antigametocyte immune responses in malaria-exposed individuals in Burkina Faso. A total of 719 blood samples were collected in a series of three cross-sectional surveys at the start, peak, and end of the wet season. The seroprevalence of antibodies with specificity for the sexual stage antigens Pfs48/45 and Pfs230 was 2-fold lower (22 to 28%) than that for an asexual blood stage antigen glutamate-rich protein (GLURP) (65%) or for the preerythrocytic stage antigen circumsporozoite protein (CSP) (54%). The youngest children responded at frequencies similar to those for all four antigens but, in contrast with the immune responses to GLURP and CSP that increased with age independently of season and area of residence, there was no evidence for a clear age dependence of responses to Pfs48/45 and Pfs230. Anti-Pfs230 antibodies were most prevalent at the peak of the wet season (P < 0.001). Our findings suggest that naturally acquired immunity against Pfs48/45 and Pfs230 is a function of recent exposure rather than of cumulative exposure to gametocytes.

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Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

et al. 2011

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“…2), the amount of Pbs48/45 produced after DNA vaccination was enough to prime an antibody response that could be further boosted by repeated parasite infections. An effective antibody response against Pbs48/45 is expected to suppress the infectivity of gametocytes in the mosquitoes (6,32). To test this, mosquitoes were fed on mice from all groups 5 days after the first infection, when P. berghei gametocytes are most infective (33).…”

Section: Resultsmentioning

confidence: 99%

“…We chose antigen Pbs48/45 from the rodent malaria parasite P. berghei for our studies as it is a well-conserved orthologue of the P. falciparum transmission-blocking vaccine candidate antigen Pfs48/45 (22,30,37,39). Both antigens Pfs48/45 and Pbs48/45 are expressed only by the sexual stage forms (gametocytes and gametes) of the corresponding species (6,21,22,32,39), and antibodies against Pfs48/45 are associated with the reduction of infectivity in mosquitoes (13,22,32,38,39). This is particularly evident in the vaccinated mice whose antibody levels had significantly decreased 6 weeks after one parasite infection but were rapidly boosted upon a second infection.…”

Section: Vol 74 2006mentioning

confidence: 99%

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Infection withPlasmodium bergheiBoosts Antibody Responses Primed by a DNA Vaccine Encoding Gametocyte Antigen Pbs48/45

2006

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An important consideration in the development of a malaria vaccine for individuals living in areas of endemicity is whether vaccine-elicited immune responses can be boosted by natural infection. To investigate this question, we used Plasmodium berghei ANKA blood-stage parasites for the infection of mice that were previously immunized with a DNA vaccine encoding the P. berghei sexual-stage antigen Pbs48/45. Intramuscular immunization in mice with one or two doses of DNA-Pbs48/45 or of empty DNA vaccine as control did not elicit detectable anti-Pbs48/45 antibodies as determined by enzyme-linked immunosorbent assay. An infection with P. berghei ANKA 6 weeks after DNA vaccination elicited comparable anti-Pbs48/45 antibody levels in mice which had been primed with DNA-Pbs48/45 or with empty DNA vaccine. However, a repeat infection with P. berghei ANKA resulted in significantly higher anti-Pbs48/45 antibody levels in mice which had been primed with the DNA-Pbs48/45 vaccine than the levels in the mock DNA-vaccinated mice. In parallel and as an additional control to distinguish the boosting of Pbs48/45 antibodies exclusively by gametocytes during infection, a separate group of mice primed with DNA-Pbs48/45 received an infection with P. berghei ANKA clone 2.33, which was previously described as a "nongametocyte producer." To our surprise, this parasite clone too elicited antibody levels comparable to those induced by the P. berghei gametocyte producer clone. We further demonstrate that the nongametocyte producer P. berghei clone is in fact a defective gametocyte producer that expresses Pbs48/45, much like the gametocyte producer clone, and is therefore capable of boosting antibody levels to Pbs48/45. Taken together, these results indicate that vaccine-primed antibodies can be boosted during repeat infections and warrant further investigation with additional malaria antigens.

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“…Pfs48/45 gene knock out experiments demonstrate a key role in male fertility [161]. Anti-Pfs48/45 antibodies in individuals naturally exposed to malaria are associated with transmission blocking activity [162] and given that it is expressed within the human host it is likely to allow natural boosting of antibody responses. Pfs25 is relatively conserved [163] while Pfs48/45 shows high levels of diversity worldwide with evidence of diversifying selection and strong geographic structuring [8,164,165].…”

Section: Pfs25 and Pfs45/48mentioning

confidence: 99%

Using Population Genetics to Guide Malaria Vaccine Design

Barry¹,

Beeson²,

Reeder³

et al. 2012

Malaria Parasites

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Association between anti‐Pfs48/45 reactivity and P. falciparum transmission‐blocking activity in sera from Cameroon

Cited by 77 publications

References 18 publications

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

Infection withPlasmodium bergheiBoosts Antibody Responses Primed by a DNA Vaccine Encoding Gametocyte Antigen Pbs48/45

Using Population Genetics to Guide Malaria Vaccine Design

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