Rhoptry-Associated Protein 1-Binding Monoclonal Antibody Raised against a Heterologous Peptide Sequence Inhibits<i>Plasmodium falciparum</i>Growth In Vitro

Moreno, Rafael; Pöltl-Frank, Friederike; Stüber, Dietrich; Matile, Hugues; Mutz, Michael; Weiss, N.; Pluschke, Gerd

doi:10.1128/iai.69.4.2558-2568.2001

Cited by 21 publications

(11 citation statements)

References 58 publications

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“…Monoclonal antibodies directed against rhoptries-associated proteins Pf RAP-1 and Pf RAP-2 have inhibited the erythrocyte invasion in vitro (Schofield et al, 1986; Harnyuttanakorn et al, 1992; Howard et al, 1998) and immunizations of Saimiri sciureus and S. boliviensis monkeys with the Pf RAP-1 and Pf RAP-2 complex demonstrated partial protection against P. falciparum (Perrin et al, 1985; Ridley et al, 1990b; Collins et al, 2000). In addition, naturally exposed individuals have shown antibodies against Pf RAP-1 conserved linear epitopes and recombinant proteins (Jakobsen et al, 1993; 1997; Stowers et al, 1997; Fonjungo et al, 1998; Moreno et al, 2001; Curtidor et al, 2004). Yet, unlike surface antigens expressed in the merozoite (the parasite stage that invades the erythrocyte), RAP-1 immunogenicity does not translate into the maintenance of observable polymorphism.…”

Section: Introductionmentioning

confidence: 99%

Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp.

Pacheco

Ryan

Poe

et al. 2010

Infection, Genetics and Evolution

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Assessing how natural selection, negative or positive, operates on genes with low polymorphism is challenging. We investigated the genetic diversity of orthologous genes encoding the rhoptry - associated protein 1 (RAP-1), a low polymorphic protein of malarial parasites that is involved in erythrocyte invasion. We applied evolutionary genetic methods to study the polymorphism in RAP-1 from Plasmodium falciparum (n= 32) and P. vivax (n= 6), the two parasites responsible for most human malaria morbidity and mortality, as well as RAP-1 orthologous in closely related malarial species found in non-human primates (NHPs). Overall, genes encoding RAP-1 are highly conserved in all Plasmodium spp. included in this investigation. We found no evidence for natural selection, positive or negative, acting on the gene encoding RAP-1 in P. falciparum or P. vivax. However, we found evidence that the orthologous genes in non-human primate parasites (P. cynomolgi, P. inui, and P. knowlesi) are under purifying (negative) selection. We discuss the importance of considering negative selection while studying genes encoding proteins with low polymorphism and how selective pressures may differ among orthologous genes in closely related malarial parasites species.

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Section: Introductionmentioning

confidence: 99%

Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp.

Pacheco

Ryan

Poe

et al. 2010

Infection, Genetics and Evolution

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“…Some antigens even induce antibodies capable to accelerate parasitegrowth (e.g. the rhoptry-associated Protein-1 [15]) or block the binding of growth-inhibitory antibodies, so called blocking antibodies, as has been described for MSP-1 [16,17]. This obstacle is overcome by the use of peptides representing those domaines of the antigen that are capable of inducing protective antibodies only and thereby avoiding the induction of antibodies with counterproductive properties, which are directed to other parts of the protein not present within the peptide.…”

Section: Optimized Malaria-antigens Delivered By Immunostimulating Rementioning

confidence: 99%

Optimized Malaria-antigens delivered by immunostimulating reconstituted influenza virosomes

Westerfeld

Pluschke

Zurbriggen

2006

Wien Klin Wochenschr

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Malaria remains a serious cause of morbidity and mortality in millions of individuals each year. The development of widespread resistance of the parasite to drugs as well as resistance of the transmitting mosquito-vector to insecticides in combination with the poor economic situation of many malaria-endemic countries make the development of an effective and inexpensive treatment and prevention a main focus of research. Vaccines remain to be one of the most cost effective and feasible means of disease control and have remarkable success in the control of many infectious disease: eradication of small pox, virtual eradication of polio and the reduction of measles and diphtheria. Next generation vaccines should focus on specific antigens rather than whole inactivated or attenuated pathogens, since the requirements by regulatory authorities concerning safety are becoming more stringent over time. But sub-unit and in particular peptide-based vaccines are poorly immunogenic themselves, and alum represents only a sub-optimal adjuvant for recombinant proteins and synthetic peptides. This emphasizes the need for suitable carrier- and adjuvant systems promoting protective immune responses by delivering protein and peptide antigens in an appropriate conformation. Here, we review the development of a new approach combining peptide-based malaria vaccine candidate antigens with an immune stimulatory carrier-system based on influenza virosomes focusing on the induction of protective antibodies.

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“…In real life, the antigen of choice is located together with several other antigens, for example, on the merozoite surface, and there might be interaction or competition between binding of different antibodies, something that is not accounted for in an ELISA. It has, for example, been shown for MSP1 that there are blocking antibodies that can compete with the binding of cleavage-inhibiting antibodies for epitopes on the merozoite [22, 23], and there are also other studies that have demonstrated that mixing of different antibodies can influence the outcome of the assay [24]. This kind of studies indicates that we should more look at using assays where the function of antibodies is studied, but the reason for why ELISAs are continued to be used to such a major extent is probably that they are very easy, fast, and robust to perform compared to functional assays.…”

Section: Elisamentioning

confidence: 99%

How Should Antibodies againstP. falciparumMerozoite Antigens Be Measured?

Chuangchaiya

Persson

2013

Journal of Tropical Medicine

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Immunity against malaria develops slowly and only after repeated exposure to the parasite. Many of those that die of the disease are children under five years of age. Antibodies are an important part of immunity, but which antibodies that are protective and how these should be measured are still unclear. We discuss the pros and cons of ELISA, invasion inhibition assays/ADCI, and measurement of affinity of antibodies and what can be done to improve these assays, thereby increasing the knowledge about the immune status of an individual, and to perform better evaluation of vaccine trials.

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Rhoptry-Associated Protein 1-Binding Monoclonal Antibody Raised against a Heterologous Peptide Sequence InhibitsPlasmodium falciparumGrowth In Vitro

Cited by 21 publications

References 58 publications

Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp.

Evidence for negative selection on the gene encoding rhoptry-associated protein 1 (RAP-1) in Plasmodium spp.

Optimized Malaria-antigens delivered by immunostimulating reconstituted influenza virosomes

How Should Antibodies againstP. falciparumMerozoite Antigens Be Measured?

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