J-LSMS 2017 | Annual Archive

JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY

Type of Vaccine

Malaria target parasite stage(s)

Mechanism of action

Reference Number

Vaccine Candidate (ID Number)

RTS, S/AS01, RTS, S/AS02

Purified recombinant circumsporozoite protein with adjuvant vaccines

Antibodies damage the sporozoite

29

Plasmodium falciparum (Pf ) circumsporozoite protein present on the sporozoite surface Several surface antigens present on whole sporozoites shortly after liver entry

surface protein present on the sporozoite surface

PfSPZ Vac, PfsPZ-C Vac

Whole sporozoite vaccines

Antibodies to gamete surface antigens block gamete development in human hosts. Antibodies to surface antigens on zygotes block development of ookinetes in moquitoes Antibodies block sporozoite entry into hepatocytes, CD8+ T cells kill any developing parasites within hepatocytes mediated CD8+ T cell responses attacking antigens expressed during liver development Radiation-attenuated Pf sporozoites induce cell-

30

Heterologous prime boost with DNA, recombinant viruses and bacteria and recombinant protein with adjuvant vaccines

Multiple component vaccines designed to induce both humoral and cellular immunity

Sporozoites before and after they enter hepatocytes

31

32, 33

Transmission blocking vaccines

Recombinant protein with adjuvant with Pf and Pv sexual

All sexual erythrocyte and mosquito stages of Pf and Plasmodium vivax (Pv) as parasites pass from human hosts to mosquitoes

erythrocyte and mosquito stages

Table 3: Some Malaria Vaccine Candidates now in Field Trials or Research and Development 29-33

CONCLUSIONS

The first peptide-based anti-sporozoite vaccine, the Patarroyo vaccine (SPf66), appeared highly effective in monkeys and humans in small-scale trials in the Colombian Amazon in the late 1980s. Unfortunately, SPf66 failed to demonstrate protection against malaria in later, larger field trials in South America and Africa. 28 Despite these early failures, the valuable field experiences with SPf66 led to the development of new similar peptide vaccine candidates targeting sporozoites, intrahepatic stages, and gametocytes. Today, malaria vaccinologists agree that any effective malaria vaccine will have to target several developmental stages in malaria’s life cycle simultaneously and require significant immune boosting with adjuvants and periodic booster injections. Table 3 describes several malaria candidate vaccines now in advanced testing and field trials as stratified by their malaria target antigens and mechanisms of action. 29-33

International travelers returning from malaria-endemic regions without takingpreventivemeasures importmost casesofmalaria into the U.S. today. Plasmodiumfalciparum , themost virulent and potentially fatal species, causes most cases. Since chloroquine resistance is now nearly universal, only chemoprophylaxis with mefloquine, atovaquone-proguanil, or doxycycline will prevent primary attacks by P. falciparum and non- falciparum species in endemic areas, but not relapsing attacks by P. vivax or P. ovale . Only primaquine can interrupt the latent hepatic or hypnozoite stages of P. vivax and P. ovale and prevent relapsing malaria. No chemoprophylactic regimen is 100% protective against malaria and must be supported by personal protective steps including applying effective topical insect repellents and avoiding mosquito bites, especially at nighttime.

138 J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017

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