Effect of anti‐mosquito antibodies on the infectivity of the rodent malaria parasite Plasmodium berghei to Anopheles farauti

Ramasamy, M. S.; Ramasamy, R

doi:10.1111/j.1365-2915.1990.tb00274.x

Cited by 43 publications

(30 citation statements)

References 20 publications

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“…Many problems of identifying suitable protective antigens are common for mosquitoes and ticks. A mosquito vaccine approach could be extremely effective if vector numbers were reduced, and parasite transmission blocked either directly (Lal et al, 1994;Ramasamy and Ramasamy, 1990) or via reducing vector longevity (Billingsley, 1994). Use of purified or partially purified antigens or a combination of antigens may give both a higher death rate and a lower fecundity rate among mosquitoes that feed on specifically sensitized host mammals.…”

Section: Archives Of Insect Biochemistry and Physiologymentioning

confidence: 98%

Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae)

Suneja

Gulia

Gakhar

2003

Arch Insect Biochem Physiol

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Rabbits were immunized three times with extracts of Anopheles stephensi midgut. Immunized rabbits showed a high titer of antibodies when characterized by ELISA. We investigated the effect of anti-mosquito midgut antibodies on mosquito fecundity, longevity, mortality, engorgement, and the development of the malaria parasite in mosquitoes. Fecundity was reduced significantly (38%) and similarly hatchability by about 43.5%. There was no statistically significant effect on mortality, longevity, and engorgement. When the mosquito blood meal contained anti-midgut antibodies, fewer oocysts of Plasmodium vivax developed in the mosquito midgut and the proportion of mosquitoes becoming infected was significantly reduced. We also found that the midgut antibodies inhibit the development and/or translocation of the sporozoites. Antisera raised against midgut of A. stephensi recognized eight polypeptides (110, 92, 70, 45, 38, 29, 15, 13 kDa) by Western blotting. Cross-reactive antigens/epitopes present in other tissues of A. stephensi were also examined both by Western blotting and in vivo ELISA. Together, these observations open an avenue for research toward the development of a vector-based malaria parasite transmission blocking vaccine and/or anti-mosquito vaccine.

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Section: Archives Of Insect Biochemistry and Physiologymentioning

confidence: 98%

Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae)

Suneja

Gulia

Gakhar

2003

Arch Insect Biochem Physiol

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“…To date, research has focused predominantly on parasite-derived molecules, such as the Pfs25 protein, which is expressed exclusively when the parasite develops in the mosquito midgut and therefore is not under selective pressure in the human host. A few reports documented the feasibility of a TBV based upon mosquito-derived molecules, using whole mosquito midgut extracts to generate transmission-blocking serum, or monoclonal antibodies in various mosquito-Plasmodium systems (7,15,16,19). In addition, it was demonstrated that antibodies that inhibit midgut trypsin activity in Aedes aegypti are capable of blocking the development of the avian parasite Plasmodium gallinaceum, suggesting that mosquito trypsin could be a target for a TBV (22).…”

Section: Discussionmentioning

confidence: 99%

Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine

et al. 2007

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Anopheles gambiae is the major African vector of Plasmodium falciparum, the most deadly species of human malaria parasite and the most prevalent in Africa. Several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (TBVs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. So far, the most promising components of a TBV are parasite-derived antigens, although targeting critical mosquito components might also successfully block development of the parasite in its vector. We previously identified A. gambiae genes whose expression was modified in P. falciparum-infected mosquitoes, including one midgut carboxypeptidase gene, cpbAg1. Here we show that P. falciparum up-regulates the expression of cpbAg1 and of a second midgut carboxypeptidase gene, cpbAg2, and that this up-regulation correlates with an increased carboxypeptidase B (CPB) activity at a time when parasites establish infection in the mosquito midgut. The addition of antibodies directed against CPBAg1 to a P. falciparum-containing blood meal inhibited CPB activity and blocked parasite development in the mosquito midgut. Furthermore, the development of the rodent parasite Plasmodium berghei was significantly reduced in mosquitoes fed on infected mice that had been immunized with recombinant CPBAg1. Lastly, mosquitoes fed on anti-CPBAg1 antibodies exhibited reduced reproductive capacity, a secondary effect of a CPB-based TBV that could likely contribute to reducing Plasmodium transmission. These results indicate that A. gambiae CPBs could constitute targets for a TBV that is based upon mosquito molecules.Malaria remains a leading cause of morbidity and mortality in human populations, with over 3 billion people living in areas at risk for malaria transmission and an estimated 350 to 500 million clinical episodes occurring annually (29). Plasmodium falciparum malaria causes more than a million deaths each year, mainly in young children in sub-Saharan Africa. Moreover, the malaria burden has increased over the last 10 to 15 years, and this situation has been associated in part with parasite resistance to commonly used antimalarial drugs and resistance of mosquito vectors to insecticides (29). Several strategies are being developed which target either the disease or its transmission. Owing to the complexity of the parasite life cycle, with both human stages that result in disease and mosquito stages that ensure transmission, an effective vaccine might combine pre-erythrocytic (sporozoite and liver stage), asexual erythrocytic, and transmission-blocking components. Although modeling of vaccine effects on malaria transmission dynamics indicates that a transmission-blocking vaccine (TBV) will be most effective in regions where the initial basic reproductive rate of malaria (R 0 ) is low (3,4,8,9), a TBV offers the advantage of blocking the spread of escape mutants that are resistant to asexual-stage ...

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“…Previous studies by us and others using polyclonal anti-midgut antibodies have shown inhibition of sporogonic development in the rodent malaria parasite, Plasmodium berghei, and the human malaria parasite, Plasmodium vivax (7)(8)(9). The aim of this study was to: (i) investigate whether mAbs against midgut antigens can block the development of two major human malaria parasites, P. falciparum and P. vivax, in several mosquito species; and (ii) determine whether anti-midgut antibodies reduce mosquito fecundity and survivorship.…”

mentioning

confidence: 99%

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship

Lal

Patterson

Sacci

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The mosquito midgut plays a central role in the sporogonic development of malaria parasites. We have found that polyclonal sera, produced against mosquito midguts, blocked the passage of Plasmodium falciparum ookinetes across the midgut, leading to a significant reduction of infections in mosquitoes. Anti-midgut mAbs were produced that display broad-spectrum activity, blocking parasite development of both P. falciparum and Plasmodium vivax parasites in five different species of mosquitoes. In addition to their parasite transmission-blocking activity, these mAbs also reduced mosquito survivorship and fecundity. These results reveal that mosquito midgut-based antibodies have the potential to reduce malaria transmission in a synergistic manner by lowering both vector competence, through transmission-blocking effects on parasite development, and vector abundance, by decreasing mosquito survivorship and egg laying capacity. Because the intervention can block transmission of different malaria parasite species in various species of mosquitoes, vaccines against such midgut receptors may block malaria transmission worldwide.O f the several hundred species of Anopheles mosquitoes worldwide, only about 20 are major vectors of human malaria. Several components contribute to this fact, including the propensity of a given species to feed on humans, the average longevity of a mosquito species, and the innate ability of a species to permit development of the parasite (i.e., vector competence). Different intervention strategies attempt to reduce malaria transmission by reducing these various components. Reducing vector competence is the primary objective behind two rapidly evolving areas of research in malaria and other vector-borne diseases, namely the replacement of natural vector populations with populations genetically engineered for refractoriness and transmission-blocking immunity (TBI).Transmission-blocking vaccines in malaria are envisioned to inhibit the developmental stages of the malaria parasites in the mosquito midgut. The first 48 h after ingestion of an infective blood meal is the most critical time period for malaria parasite development within the mosquito. It is during this time that the parasite fertilization takes place and the resulting zygotes transform into motile ookinetes. Ookinetes traverse the midgut and lodge between the basal lamina and midgut epithelia, where they encyst and develop into sporozoite-producing oocysts.Several studies with rodent and human malaria parasites have revealed that the ookinete-to-oocyst transition is the most vulnerable link in sporogonic development of malaria parasites (1-3). Thus, the developing parasite stages in the mosquito midgut provide an ideal target for transmission-blocking vaccines. Efforts in transmission-blocking vaccines in malaria have focused primarily on the use of specific parasite antigens as targets of immune intervention in the mosquito midgut. Antibodies against parasite antigens block fertilization and͞or prevent the movement of ookinetes across the...

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Effect of anti‐mosquito antibodies on the infectivity of the rodent malaria parasite Plasmodium berghei to Anopheles farauti

Cited by 43 publications

References 20 publications

Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae)

Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae)

Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine

Anti-mosquito midgut antibodies block development of Plasmodium falciparum and Plasmodium vivax in multiple species of Anopheles mosquitoes and reduce vector fecundity and survivorship

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