A recent editorial in the New England Journal of Medicine summarized the current state of malaria vaccines (Clemens J, Moorthy V. Implementation of RTS,S/AS01 malaria vaccine — the need for further evidence. N Engl J Med. 2016 Jun 30;374(26):2596-7).
In 2015, an estimated 438,000 people died from malaria. Most of these deaths occurred in young African children and most were caused by Plasmodium falciparum. Because malaria is one of the biggest killers of children in the world, a successful vaccine would be an important tool in the fight against this disease. The most advanced of the current candidate malaria vaccines is RTS,S/AS01: a recombinant vaccine that fuses the pre-erythrocyte circumsporozoite protein of P. falciparum with the hepatitis B surface antigen. This fusion protein is adjuvanted with a combination of monophosphoryl lipid A (which is the adjuvant that was used in the HPV vaccine, Cervarix®) and saponin.
A recent study of the RTS,S/AS01 vaccine funded by the Bill and Melinda Gates Foundation examined the efficacy of a three- or four-dose schedule in infants who received their first dose of vaccine between 6 to 12 weeks of age or 5 to 17 months of age. Vaccinations were given monthly and children were followed up for four years (RTS,S Clinical Trials Partnership. Efficacy and safety of RTS.S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of the phase 3, individually randomized, controlled trial. Lancet. 2015 Jul 4;386(9988):31-45.) For those who received the first dose at 5 to 17 months of age, the magnitude of protection against severe malaria was 1 percent in the three-dose group and 32 percent in the four-dose group and waned rapidly to no protection 20 months after the first dose in either group. Although these efficacy data fall far short of most childhood vaccines, the impact would still be considerable in countries with a high burden of disease. For children whose first vaccine was administered between 6 and 12 months of age, the protective efficacy was lower than in the 5- to 17-month group following either the three- or four-dose regimen.
The World Health Organization (WHO) has given support only for the four-dose regimen in children whose first dose is given between 5 and 17 months of age. The WHO is also requesting more evidence for efficacy in countries in sub-Saharan Africa with moderate to high levels of malaria transmission.