New malaria vaccine described as “complementary”

20 Jan 2010

Patrick Adams

Source: TropIKA.net

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A male Plasmodium falciparum gametocyte in the mosquito gut. A vaccine is to be developed that will be active against this stage of the malarial parasite’s development. WHO/MAP/TDR.

The announcement (see TropIKA.net Blog) that PATH MVI will partner with the Sabin Institute and the Johns Hopkins Bloomberg School of Public Health (JHBSP) to develop a malaria “transmission-blocking vaccine” (TBV) represents a new and exciting direction in malaria control. In combination with other interventions, the vaccine, which aims to inhibit the development of the parasite in the mosquito, may well serve as a potent tool for the eventual eradication of the disease.

However, though it may indeed block transmission, Chris Plowe, Pedro Alonso and Stephen Hoffman argue that the term TBV is something of a misnomer.

In an editorial titled published in the December issue of the Journal of Infectious Diseases, the researchers wrote, “There are two approaches to developing a vaccine that would prevent transmission of P. falciparum. The first approach is to prevent the development of gametocyes in humans.” This can be done, they explain, “by inducing immune responses against sporozoites and/or infected hepatocytes, thereby preventing the full development of schizonts in the liver.” To date, studies of the preerythrocytic PfSPZ vaccine, currently being developed by Sanaria Inc, are the only source of data proving that this can be done – see TropIKA.net article.

The other approach, they write, is to block transmission of parasites to mosquitoes “by inducing immune responses against the sexual stages of the parasites (i.e. gametocytes and gametes) and/or the mosquito stages of the parasites.” This is what the MVI-Sabin-JHBSP vaccine aims to do. And although it could be an effective elimination/eradication tool, write the researchers, “this type of vaccine, by itself, would not prevent disease in the infected individual”.

“A mosquito and sexual stage vaccine is a transmission-blocking vaccine,” Hoffman said in a recent interview. “But if somehow you had a blood-stage vaccine, that would be a transmission-blocking vaccine also.” Indeed, what is often referred to as a “transmission blocking” vaccine is one that only works on transmission.

“I personally believe that without something else that will be hard to sell, partly because, in order to have a significant impact, you’re going to have to immunize a large percentage of the population,” he said. “It’s not just infants who are transmitting malaria; everybody can transmit.”

But there’s another, arguably more important, obstacle that is seldom discussed, he says. “A mosquito can only inject, say, a 100 or 300 sporozoites – and mosquitoes usually have a few thousand in them. What happens if your vaccine reduces the infection by 80% in the individual mosquito? That mosquito still has a few hundred sporozoites in their salivary gland when they feed. We don’t know that that will change their capacity to transmit malaria.”

Hoffman says that his company Sanaria is developing its whole parasite sexual and mosquito stage vaccine “...because we can actually do it. We don’t need an individual protein here. And that’s where this field began, with three papers (2-4) in the 1970s and 80s that showed that you could take the sexual stage of P. berghei and immunize with it in an adjuvant and get this transmission-blocking activity.”

Hoffman sees such a vaccine as being complementary to an effective pre-erythrocytic-stage vaccine. A vaccine that could achieve 90% protection at the pre-erythrocitic stage and 90% protection at the sexual and mosquito stage would confer 99% protection overall. “That would be a heck of an impact on transmission. I think that it’s worthwhile to pursue. I don’t see it as a stand-alone intervention.”

References

1. Plowe C, Alonso P, Hoffman S (2009). The potential role of vaccines in the elimination of falciparum malaria and the eventual eradication of malaria. J Infect Dis; 200(11):1646-1649. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19877844

2. Carter R, Chen DH (1976). Malaria transmission blocked by immunisation with gametes of the malaria parasite. Nature; 263(5572):57-60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/986561

3. Gwadz RW (1976). Successful immunization against the sexual stages of Plasmodium gallinaceum. Science; 193(4258):1150-1151. Available from: http://www.ncbi.nlm.nih.gov/pubmed/959832

4. Mendis KN, Targett GA (1979) Immunisation against gametes and asexual erythrocytic stages of a rodent malaria parasite. Nature; 277(5695):389-391. Available from: http://www.ncbi.nlm.nih.gov/pubmed/551260