Date Published: January 25, 2011
Publisher: Public Library of Science
Abstract: The Malaria Eradication Research Agenda (malERA) Consultative Group on Vaccines present a research and development agenda to provide the tools to create vaccines that may be used during malaria eradication.
Partial Text: Vaccines are the most cost-effective tools for public health and have been instrumental in previous elimination campaigns against smallpox , polio , and measles ,. Vaccines have also been useful for sustained control of diseases such as neonatal tetanus , and vaccines such as Haemophilus influenzae type b conjugate vaccine have the potential to lead to elimination in some settings .
First, we introduce the broad concept of VIMT. VIMT may be composed of one or more of the following components: classical TBVs that target sexual and mosquito stage parasite antigens; highly effective pre-erythrocytic vaccines that reduce asexual and sexual stage parasite prevalence rates; highly effective asexual erythrocytic stage vaccines that inhibit multiplication of asexual stage parasites efficiently to reduce blood-stage parasite densities and have an impact on malaria transmission; and vaccines that target vector antigens to disrupt parasite development in the vector. It seems obvious that a highly effective pre-erythrocytic vaccine that prevents erythrocytic stage infection will reduce transmission, but the effect of partially effective pre-erythrocytic or asexual blood-stage vaccines on individual infectivity needs investigation. A successful VIMT must primarily reduce malaria transmission. However, VIMTs that include pre-erythrocytic and/or asexual blood-stage vaccine components may also provide individuals with protection against malaria. Such VIMT would also protect the population against epidemic spread following reintroduction of malaria after elimination, an important characteristic given that the gains accrued through many years of elimination can be rapidly reversed if malaria is reintroduced to a population with no antimalarial immunity .
A TPP is an industry-standard tool that gives clear guidance on the critical characteristics of a candidate product under development. TPPs are developed early in the development process and ensure that research and development efforts are focused on those activities that are necessary to develop a product that will meet the needs of end users. Table 1 presents a TPP for VIMT. For each characteristic in this TPP, we propose a “desired target” (aspirational) and a “minimally acceptable target” (must achieve). A vaccine candidate that does not meet or exceed most, if not all, of the minimally acceptable targets is likely to have a significantly reduced likelihood of successful introduction and uptake.
Much of the ongoing work on malaria vaccine development has focused on the development of interventions that address disease manifestations and the work has been primarily focused on P. falciparum. To support the development of vaccines and other tools necessary for malaria eradication new dimensions need to be added to the fundamental research portfolio (see  also). For example, P. vivax needs to be added, and efforts need to be refocused on the development of vaccines that target sexual and mosquito stages of malaria parasites, which should interrupt transmission. The expanded portfolio also needs to include more research on vaccine delivery systems and adjuvants, the transmission dynamics and population biology of malaria parasites, and measurements of transmission rates.
Vaccines can play a key role in multisectoral efforts to eliminate and eventually eradicate malaria. Current efforts to develop malaria vaccines are primarily focused on reducing infection rates, blocking replication of the parasite in the bloodstream, and the pathologic effects of the parasite in individuals, thereby reducing malaria morbidity and mortality in vaccinated individuals. Some of these vaccines, if highly effective, may also reduce transmission. These efforts need continued support.