Robert Fortner

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ArsTechnica: The difficult search for a malaria vaccine | 

Seattle writer Robert Fortner, in ArsTechnica, examines how far we have come in the search for an effective malaria vaccine.

This story is focused on what many consider the most promising malaria vaccine candidate, called RTS,S, made by GlaxoSmithKline decades ago and being tested (again) under improved formulations with funding from the Bill & Melinda Gates Foundation and the PATH Malaria Vaccine Initiative. As I’ve noted before, many experts are quietly expressing doubt RTS,S will work even though it has provided some new insights into the immunology of malaria.

Bob digs deeper into the evidence:

Photo by Caitlin Kleiboer

Testing the RTS/S malaria vaccine in Malawi

After clean water, vaccines may have saved more lives than any other public health intervention. Eradication of malaria, a disease that may have killed more humans than any other single cause, likely requires a malaria vaccine.

However, after nearly a century of research, today’s only candidate might not pack enough immunological punch to win deployment. Sadly, there are no obvious successors. Goals for vaccines set in 2006 are now approaching, but may not be possible to meet.

A quarter century of painstaking work has gone into the vaccine known as RTS,S, now in phase III clinical trials. But after numerous modifications and enhancements, RTS,S still protects only intermittently, 30 to 60 percent of the time.

This protection wanes, although over how many years or months is still being studied. The vaccine reduces disease but, so far, not deaths.

The organism that causes malaria has made vaccine development a challenge. Malaria is caused by the parasite Plasmodium rather than bad or “mal” air as thought long ago. The human genome, particularly in sub-Saharan Africa, chronicles our lengthy and ongoing battle with Plasmodium.

Strong selection pressure on humans has led to evolutionary gambits like the sickle cell trait—risking potentially lethal blood disorders to reduce susceptibility to malaria infection. But Plasmodium has kept the upper hand in many ways. The parasite continues to baffle the immune system with a complex genome reshuffled by sexual reproduction, a multi-stage life cycle that features antigenic shape-shifting, to avoid immune surveillance.

For pathogens like polio, the human immune system can develop durable, sterilizing immunity, which rids the body of the invader. Polio vaccines reliably trigger these natural mechanisms. For malaria, humans can acquire a kind of immunity and potentially even clear parasites completely. But the genetic diversity of Plasmodium falciparum allows it to often avoid such direct hits.

Acquired immunity is often a détente in which the parasite survives and reproduces at low levels that cause neither disease nor death. A study in western Kenya, for example, found 90 percent of a cohort was infected with falciparum even though not one of the 93 people was ill. Vaccines like RTS,S prod the immune system toward this partial protection, but there is concern that it isn’t reducing severe malaria enough.

Continue reading at ArsTechnica.