The March Toward Malaria Vaccines

Abstract

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria.

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

“…An effective vaccine against malaria for humans is not yet available (Hoffmann et al 2015;Miura 2016). The RTS,S/ AS01vaccine has been considered as the most advanced vaccine candidate, but the WHO has recently not recommended its inclusion in the Expanded Programme of Immunizations (Birkitt 2016;Gosling and von Seidlein 2016).…”

Differential miRNA Expression in the Liver of Balb/c Mice Protected by Vaccination during Crisis of Plasmodium chabaudi Blood-Stage Malaria

“…A vaccine for an effective and reliable anti-malaria prophylaxis is not yet available, despite enormous efforts during the last 35 years (Halbroth and Draper, 2015; Hoffman et al, 2015; Miura, 2016). Until recently, the RTS,S/AS01 has been regarded as the most advanced vaccine candidate.…”

Antigenicity of a Bacterially Expressed Triple Chimeric Antigen of Plasmodium falciparum AARP, MSP-311 and MSP-119: PfAMSP-Fu35

“…These mainly include use of naked DNA, viral vectors to deliver relevant DNA sequences, prime/boost DNA vaccines that include recombinant DNA, viruses and proteins, vaccines based on whole sporozoite, synthetic peptides and recombinant protein(s) with adjuvant [13]. In principle DNA based vaccines are most attractive in that they are simple to design with a possibility of including multiple B and T cell epitopes from different antigens, easy to produce and do not require strong adjuvants to generate significant immune response particularly cellular responses.…”

“…However, many multiple epitope based DNA vaccines did not live up to expectations and currently there is no DNA vaccine that has been commercialized. A naked DNA based vaccine comprising of PfCSP failed to induce any significant immune responses in human trials [13]. Heterologous prime/boost vaccine strategy is another attractive approach being used in developing vaccines against malaria.…”