Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys

De, Sai Lata; Stanisic, Danielle I.; Breda, Karin van; Bellete, Bernadette; Harris, Ivor; McCallum, Fiona; Edstein, Michael D.; Good, Michael F.

doi:10.1016/j.ijpara.2016.05.002

Cited by 10 publications

(10 citation statements)

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“…A proliferative CD8 ϩ T cell response was induced following immunization with a single dose of TF-A-attenuated P. falciparum. Although only limited protection was seen in this model (44), further vaccine doses may improve protection.…”

Section: Chemical Attenuation Of Malaria Parasites In Vitromentioning

confidence: 72%

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Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine

2017

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Malaria vaccine development has been dominated by the subunit approach; however, many subunit vaccine candidates have had limited efficacy in settings of malaria endemicity. As our search for an efficacious malaria vaccine continues, the development of a whole-organism vaccine is now receiving much scrutiny. One strategy currently being explored in the development of a whole-organism vaccine involves chemical attenuation of the malaria parasite. In vivo and in vitro chemical attenuation of both liver-stage and blood-stage Plasmodium parasites has been investigated. Here, we discuss both approaches of chemical attenuation in the development of a whole-organism vaccine against malaria.KEYWORDS chemical attenuation, malaria, whole-organism vaccine C urrent methods in malaria control, such as the use of indoor residual spraying, insecticide-treated nets, and drug therapies, have led to reductions in malaria cases and malaria-related deaths (1). However, malaria still remains a leading cause of morbidity and mortality, with 3.3 billion people at risk of becoming infected with Plasmodium parasites (1). In 2015 alone, there were 212 million clinical cases and approximately 429,000 deaths due to malaria (2); therefore, the need for an efficacious malaria vaccine remains prominent. However, despite concerted efforts over many years, an effective malaria vaccine remains elusive. There have been continued concerns with the efficacy of the subunit vaccine approach (3-6), leading to a renewed interest in the use of the whole-organism vaccine approach for malaria.Whole-organism vaccines have been used successfully to protect individuals and populations from infectious diseases (reviewed in reference 7). This approach maximizes the number of antigens presented to the immune system and thus may limit the impact of antigenic diversity on vaccine efficacy. There are different types of wholeorganism vaccines, including killed and live attenuated vaccines, that can be produced using heat, genetic manipulation, radiation, or chemicals. Some of the earliest vaccines utilized formalin to chemically treat the infectious organism (reviewed in reference 8). These vaccines are often referred to as "inactivated" vaccines and include vaccines against polio, hepatitis A, and cholera (9-11). More recently, chemicals have been used as attenuating agents in the development of a malaria vaccine, with promising results. CHEMICAL ATTENUATION OF MALARIA PARASITES IN VIVOSome of the earliest evidence that protection could be induced by infection and drug cure in malaria was provided by antimalaria drug evaluation studies in monkeys (12) and studies using malaria therapy in patients with neurosyphilis (13,14). Although not the primary aim of these studies, they demonstrated that drug cure given after a patent primary infection induced protection against a subsequent secondary infection, (12)(13)(14). Since these initial studies were conducted, numerous studies (in animals and humans) have focused on the protection and immunity induced by a ...

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Section: Chemical Attenuation Of Malaria Parasites In Vitromentioning

confidence: 72%

“…Further preclinical studies have been conducted using chemically attenuated bloodstage P. falciparum strain FVO parasites administered to Aotus nancymaae monkeys (44). A proliferative CD8 ϩ T cell response was induced following immunization with a single dose of TF-A-attenuated P. falciparum.…”

Section: Chemical Attenuation Of Malaria Parasites In Vitromentioning

confidence: 99%

Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine

2017

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“… 17 , 18 , 20 These vaccines activated peripheral blood CD8 + T cells but did not confer cross-stage protection, and blood-stage protection remained intact after CD8 + T cell depletion. 17 Similar findings in Aotus nancymae monkeys 21 prompted a pilot study in humans to assess safety and immunogenicity of P . falciparum blood-stage parasites chemically attenuated in vitro (reviewed in Stanisic and Good manuscript in preparation ).…”

Section: Blood Stage Vaccinesmentioning

confidence: 80%

Advances in malaria vaccine development: report from the 2017 malaria vaccine symposium

et al. 2017

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The Malaria Vaccine Symposium occurred at Johns Hopkins University in Baltimore, MD, USA on April 25th, 2017, coinciding with World Malaria Day and the WHO announcement that the RTS,S malaria vaccine would begin pilot implementation programs in Ghana, Kenya, and Malawi in 2018. Scientists from several disciplines reported progress on an array of malaria vaccine concepts and product candidates, including pre-erythrocytic vaccines that prevent infection, blood-stage vaccines that limit infection and disease, and transmission-blocking vaccines that interrupt the spread of infection. Other speakers highlighted the immunological and genetic considerations that must be addressed by vaccinologists to yield the most efficacious vaccines. Here, we highlight the advances in malaria vaccinology that were reported at the symposium.

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“…There are several attenuation approaches utilized in whole malaria parasite vaccine development, of note is the ability to attenuate the parasite using chemical treatment. This has produced encouraging results, with homologous and heterologous protection observed in rodent models and cell-mediated responses in non-human primates [63][64][65][66]. How then can we exploit the delayed death phenotype for vaccine development?…”

Section: Utilization Of the Delayed Death Phenotype In Vaccine Develomentioning

confidence: 99%

Exploiting the apicoplast: apicoplast-targeting drugs and malaria vaccine development

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2018

Microbes and Infection

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Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys

Cited by 10 publications

References 45 publications

Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine

Chemical Attenuation in the Development of a Whole-Organism Malaria Vaccine

Advances in malaria vaccine development: report from the 2017 malaria vaccine symposium

Exploiting the apicoplast: apicoplast-targeting drugs and malaria vaccine development

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