Two separate phase II trials of an experimental malaria vaccine in infants and young children in Africa have published promising results this week and researchers are hopeful that once regulatory approval comes through they can press ahead with phase III trials of GlaxoSmithKline (GSK) Biologicals’ RTS,S/AS vaccine candidate in Africa.

The trials, which were conducted in Kenya and Tanzania, are part of a global effort to develop a malaria vaccine under the auspices of the PATH Malaria Vaccine Initiative (MVI). The findings were published online in two separate studies in the 8 December issue of the New England Journal of Medicine, NEJM and were also presented on that date at the 57th annual meeting of the American Society for Tropical Medicine and Hygiene (ASTMH) in New Orleans.

Every year, malaria kills nearly 1 million people worldwide, most of them babies and small children in Africa, for whom the vaccine is designed.

RTS,S/AS is the leading candidate in the PATH MVI program, and the trial data shows that the experimental vaccine provides both infants and children with significant protection against malaria. In infants, the trial showed for the first time that the candidate vaccine can be given as part of national immunization programs in Africa.

The candidate RTS,S/AS01 reduced the risk of clinical episodes of malaria in children aged from 5 to 17 months by 53 per cent over 8 months of follow up and also showed promising results on the safety tests.

Director of MVI, Christian Loucq, said that the trial results showed that the investment in malaria vaccine development was starting to pay off.

“We are closer than ever before to developing a malaria vaccine for children in Africa,” said Loucq.

“History has shown that vaccines are the most powerful tool to control and eliminate infectious diseases. Clearly, the world urgently needs a safe and effective vaccine to win the war against this terrible disease,” he added.

The studies build on earlier work on the efficacy of RTS,S/AS which was published in the Lancet in 2007, including a phase II trial that showed “proof of concept” that the candidate vaccine had the potential to prevent infants from being infected with malaria.

Co-inventor of the vaccine and vice president for Research and Development, Emerging Diseases and HIV at GSK Biologicals, Joe Cohen, said that everyone was highly motivated with energy levels at an “all time high” as they anticipate the launch of the phase III trial early next year.

Cohen said that the candidate vaccine works alongside the standard infant vaccines of the World Health Organization (WHO) Expanded Program of Immunization (EPI). It has a good safety profile, and significantly consistent level of efficacy, he added.

The infant study which was conducted in Tanzania, involved 340 babies under 12 months old and found that when given at 8, 12 and 16 weeks with a commonly used childhood vaccine, RTS,S/AS02 did not interfere with the immune response of any of the vaccine components, which contained antigens for Diphtheria (D), Tetanus (T), whole-cell pertussis (Pw) and heamophilus influenzae B (Hib).

The results showed a 65 per cent reduction against first infection from malaria in those babies that were given three doses of the candidate vaccine and were followed for 6 months. This confirmed earlier findings published in October last year when the vaccine was given in a staggered fashion with other childhood vaccines.

The other trial, which took place in Kenya and Tanzania, involved 894 children aged from 5 to 17 months and evaluated the safety and efficacy of the RTS,S/AS candidate vaccine with another GSK Adjuvant System childhood vaccine called AS01. The study was designed as a double blind randomized trial where children were given either three doses of the candidate vaccine or a rabies vaccine.

The results showed that the RTS,S/AS01 combination reduced clinical episodes of malaria by 53 per cent for up to an average follow up of 8 months. These findings are even better than an earlier trial in Mozambique with GSK’s AS02 that showed a 35 per cent efficacy.

Funding for the development of this vaccine has come from the Bill and Melinda Gates Foundation and GSK.

“Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants.”
Abdulla, Salim, Oberholzer, Rolf, Juma, Omar, Kubhoja, Sulende, Machera, Francisca, Membi, Christopher, Omari, Said, Urassa, Alwisa, Mshinda, Hassan, Jumanne, Ajuza, Salim, Nahya, Shomari, Mwanjaa, Aebi, Thomas, Schellenberg, David M., Carter, Terrell, Villafana, Tonya, Demoitie, Marie-Ange, Dubois, Marie-Claude, Leach, Amanda, Lievens, Marc, Vekemans, Johan, Cohen, Joe, Ballou, W. Ripley, Tanner, Marcel.
N Engl J Med Published online on 8 December 2008.
DOI: 10.1056/NEJMoa0807773.

Click here for Article.

“Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age.”
Bejon, Philip, Lusingu, John, Olotu, Ally, Leach, Amanda, Lievens, Marc, Vekemans, Johan, Mshamu, Salum, Lang, Trudie, Gould, Jayne, Dubois, Marie-Claude, Demoitie, Marie-Ange, Stallaert, Jean-Francois, Vansadia, Preeti, Carter, Terrell, Njuguna, Patricia, Awuondo, Ken O., Malabeja, Anangisye, Abdul, Omar, Gesase, Samwel, Mturi, Neema, Drakeley, Chris J., Savarese, Barbara, Villafana, Tonya, Ballou, W. Ripley, Cohen, Joe, Riley, Eleanor M., Lemnge, Martha M., Marsh, Kevin, von Seidlein, Lorenz.
N Engl J Med Published online on 8 December 2008.
DOI: 10.1056/NEJMoa0807381

Click here for Article.

Sources: Malaria Vaccine Initiative.

Written by: Catharine Paddock, PhD