Efficacy model for mosquito stage transmission blocking vaccines for malaria

Saul, Allan

doi:10.1017/s0031182008000280

Cited by 31 publications

(36 citation statements)

References 23 publications

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“…In the DBA/2 strain of mice lacking a component of the complement system, the number of oocysts formed is significantly increased in feeding mosquitoes (26); however, anopheline mosquitoes collected in field are usually not as heavily infected, and a single oocyst is commonly detected. Therefore, a more moderate antibody level may confer effective transmission-blocking immunity in humans (21).…”

Section: Discussionmentioning

confidence: 99%

Malaria Ookinete Surface Protein-Based Vaccination via the Intranasal Route Completely Blocks Parasite Transmission in both Passive and Active Vaccination Regimens in a Rodent Model of Malaria Infection

et al. 2009

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Malaria vaccines based on ookinete surface proteins (OSPs) of the malaria parasites block oocyst development in feeding mosquitoes and hence disrupt the parasite life cycle and prevent the disease from being transmitted to other individuals. To investigate whether a noninvasive mucosal vaccination regimen effectively blocks parasite transmission in vivo, Plasmodium yoelii Pys25, a homolog of the Pfs25 and Pvs25 OSPs of Plasmodium falciparum and Plasmodium vivax, respectively, was intranasally (i.n.) administered using a complement-deficient DBA/2 mouse malaria infection model, in which a highly elevated level of oocysts develops in feeding mosquitoes. Vaccinated mice developed a robust antibody response when the vaccine antigen was given together with cholera toxin adjuvant. The induced immune serum was passively transferred to DBA/2 mice 3 days after infection with P. yoelii 17XL, and Anopheles stephensi mosquitoes were allowed to feed on the infected mice before or after serum transfusion. This passive immunization completely blocked oocyst development; however, immune serum induced by the antigen or adjuvant alone did not have such a profound antiparasite effect. Further, when i.n. vaccinated mice were infected with the parasite and then mosquitoes were allowed to directly feed on the infected mice, complete blockage of transmission was again observed. To our knowledge, this is the first time that mucosal vaccination has been demonstrated to be efficacious for directly preventing parasite transmission from vaccinated animals to mosquitoes, and the results may provide important insight into rational design of nonparenteral vaccines for use against human malaria.Malaria is one of the most important infectious diseases, and the levels of mortality and morbidity are high, especially among children in developing countries in Africa, Asia, and South America. Implementation of malaria control measures, such as antimalaria drug chemotherapy and insecticide-treated bed nets, has made a significant contribution to reducing the incidence of malaria in many parts of the world. However, these control measures may not be sufficient, and therefore new tools, including vaccines, should be included in a new malaria control campaign for local elimination and final eradiation of malaria from the globe (7). A promising strategy to counteract global malaria endemicity is to develop highly efficacious vaccines, and several promising candidates have been intensively investigated (7,20); vaccines targeting asexual stages (i.e., sporozoite, hepatic, and erythrocytic stages) are designed to prevent infection and reduce disease severity, while vaccines that target the sexual stage, in which the parasite undergoes sporogonic development in anopheline mosquitoes, prevent vector-mediated transmission of the parasite from person to person (4,8,14,17,25). Although transmission-blocking vaccines do not directly prevent infection, they reduce parasite infectivity for the vector and consequently lower the mosquito infection rate and the freque...

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Section: Discussionmentioning

confidence: 99%

Malaria Ookinete Surface Protein-Based Vaccination via the Intranasal Route Completely Blocks Parasite Transmission in both Passive and Active Vaccination Regimens in a Rodent Model of Malaria Infection

et al. 2009

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“…The SMFA has traditionally been evaluated in terms of the reduction in oocyst density compared to controls [69] which gives reproducible results for potent antibody concentrations [70,71]. However, high densities of gametocytes as used in the SMFA and related oocyst densities are not representative for natural infections [70][71][72][73][74][75]. It is, therefore, difficult to directly translate SMFA outcomes on a density scale to a predicted impact on malaria transmission in the community [74,76].…”

Section: The Standard Membrane Feeding Assaymentioning

confidence: 99%

“…Evidence from the field and transmission models indicate that the public health impact of SSM-VIMTs can be expected over all levels of transmission intensity [75,81]. This will lead to a reduced incidence of infections in all endemic areas and can accelerate the path to elimination in low endemic settings (e.g.…”

Section: Public Health Impact Of Ssm-vimtmentioning

confidence: 99%

Transmission blocking malaria vaccines: Assays and candidates in clinical development

Sauerwein

Bousema

2015

Vaccine

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Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT.

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“…First, current evidence suggests that the levels of antibody in blood that would be required to significantly affect mosquito development may need to be extremely high (107). Conjugation of Pfs25 to a carrier such as outer membrane protein complex (OMPC) of Neisseria meningitides serogroup B may overcome this problem, as the conjugate induces high-titer antibody in rhesus monkeys that persists for at least two years (108).…”

Section: Transmission-blocking Vaccinesmentioning

confidence: 99%

Advances and challenges in malaria vaccine development

Crompton

Pierce²,

Miller³

2010

J. Clin. Invest.

236

189

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Malaria caused by Plasmodium falciparum remains a major public health threat, especially among children and pregnant women in Africa. An effective malaria vaccine would be a valuable tool to reduce the disease burden and could contribute to elimination of malaria in some regions of the world. Current malaria vaccine candidates are directed against human and mosquito stages of the parasite life cycle, but thus far, relatively few proteins have been studied for potential vaccine development. The most advanced vaccine candidate, RTS,S, conferred partial protection against malaria in phase II clinical trials and is currently being evaluated in a phase III trial in Africa. New vaccine targets need to be identified to improve the chances of developing a highly effective malaria vaccine. A better understanding of the mechanisms of naturally acquired immunity to malaria may lead to insights for vaccine development.

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Efficacy model for mosquito stage transmission blocking vaccines for malaria

Cited by 31 publications

References 23 publications

Malaria Ookinete Surface Protein-Based Vaccination via the Intranasal Route Completely Blocks Parasite Transmission in both Passive and Active Vaccination Regimens in a Rodent Model of Malaria Infection

Malaria Ookinete Surface Protein-Based Vaccination via the Intranasal Route Completely Blocks Parasite Transmission in both Passive and Active Vaccination Regimens in a Rodent Model of Malaria Infection

Transmission blocking malaria vaccines: Assays and candidates in clinical development

Advances and challenges in malaria vaccine development

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