Towards Eradication of Malaria: Is the WHO’s RTS,S/AS01 Vaccination Effective Enough?

Abstract

Background: Recent advances in mosquito eradication and antimalarial treatments have reduced the malaria burden only modestly. An effective malaria vaccine remains a high priority, but its development has several challenges. Among many potential candidates, the RTS,S/AS01 vaccine (Mosquirix TM) remains the leading candidate. Objective and Method: This review aims to understand the advances in the RTS,S/AS01 vaccine, and future comments regarding the vaccine's effectiveness in malaria eradication. Literature review for the past five decades was performed searching PubMed, EMBASE Ovid, and Cochrane Library, with using the following search items: ("malaria" OR "WHO's malaria" OR "Plasmodium falciparum" OR "RTS,S" OR "RTS,S/AS01" OR "RTS,S/AS02" OR "pre-erythrocytic malaria" OR "circumsporozoite" OR "Mosquirix") AND ("vaccine" OR "vaccination"). Results: RTS,S/AS01, a recombinant pre-erythrocytic vaccine containing Plasmodium falciparum surface-protein (circumsporozoite) antigen, is safe, well-tolerated, and immunogenic in children. Three doses, along with a booster, have a modest efficacy of about 36% in children (age 5-17 months) and about 26% in infants (age 6-12 weeks) against clinical malaria during a 48-month follow-up. However, the efficacy varies among population subgroups and with the parasite strain, it reduces without a booster and offers protection for a limited duration. Because of its potential cost-effectiveness and positive public health effect, the vaccine is being investigated in a pilot program for mortality benefits and broader deployment. Conclusion: The RTS,S/AS01 vaccine prevents malaria; however, it should be considered another addition to the malaria-control program and not as an eradication tool because of its relatively low to modest efficacy.

Ethical considerations for introducing RTS,S/AS01 in countries with moderate to high Plasmodium falciparum malaria transmission

“…1 This recommendation was made despite RTS,S showing only a 30% reduction in preventing deadly severe malaria, falling short of the WHO effectiveness threshold of 75%, and in light of promising vaccinessuch as the R21/Matrix-M-under clinical development. [2][3][4] Over the coming weeks and months, health ministers and government officials across sub-Saharan Africa and beyond will have to decide whether to introduce RTS,S into their national immunisation programmes and feature the vaccine as part of their national strategy to eliminate malaria. 5 If RTS,S was highly effective at preventing malaria, such a decision would be easy to make.…”

Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

“…Current existing data revealed that the RTS, S/AS01 vaccine is safe, well tolerated, and immunogenic in children. Although it prevents malaria, its efficacy is modest, showing about a 26% efficacy in infants and a 36% efficacy in children in the four-year follow-up [176,177]. In contrast, herpes zoster is caused by reactivation of the latent varicella zoster virus from a previous infection, which is more likely to occur in people with age-related declines in immunity or in immune-suppressed populations.…”

Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges

“…These challenges related to chemotherapy and vector control have enforced the malaria research community to look for an effective malaria vaccine as high priority. However, despite many potential candidates on development, the hope for an effective and widely available vaccine seems to be challenging due to several factors ranging from the complex nature of the parasite to the cost of the developed vaccine [ 6 ].…”