Although it is more than 200 years since Jenner’s pioneering work on vaccination, there are still many infectious diseases that resist the development of effective vaccines. Somewhat shockingly, despite years of research effort, there are still no highly effective vaccines against human parasitic diseases. Malaria, the most problematic of these, kills more than half a million people each year—many of these infants and children, qualifying the mosquito that transmits the parasite as one of the most dangerous creatures on earth. Not surprisingly then, recent hopeful news of an anti-malaria vaccine that appears to protect against the disease has been greeted with enthusiasm.
The search for an effective anti-malaria vaccine has been fraught with difficulty due to the complex life cycle of the parasite (Plasmodium falciparum and other Plasmoduim species), compounded by its propensity to change its surface composition and develop resistance to various treatment efforts. The parasite thus presents an ever-changing target for treatment efforts. In the absence of an effective vaccine, anti-malarial efforts have been dependent on drug treatment (also liable to development of resistance), eradication programs, and preventive measures such as insecticide-laced mosquito netting.
The life cycle of the parasite spans both human and insect hosts. Initial infection occurs when Plasmodium sporozoites are released from the salivary glands of the female mosquito into the human bloodstream via the insect bite. The sporozoites then invade liver cells where they multiply and differentiate into merozoites, which are released into the bloodstream where they invade and multiply in red blood cells, causing the fevers, chills and other miserable symptoms of the disease. Thereafter gametocytes are produced, and these are subsequently ingested by mosquitos during a blood meal, perpetuating the life cycle. In the female mosquito gut, the gametocytes undergo fertilization and develop into sporozoites.
A life cycle of this complexity makes vaccine development a challenge, raising issues such as which stage of the life cycle to target, and offering a vast array of ever changing surface proteins to sort through in search of potential vaccine components. Efforts over the past decades have tested attenuated sporozoite vaccines delivered via insect bite, sporozoite surface antigens combined with hepatitis virus as a delivery vehicle, and vaccines designed to elicit serum antibodies that prevent transmission of gametocytes from the human host to the mosquito. Some have looked promising, only to result in short-lived protection, and none have yet resulted in high levels of protection of subjects in clinical trials.
The recent study, which was published in the August 9 issue of Science, details promising initial results from a small study using an attenuated sporozoite vaccine. The authors used attenuated sporozoites harvested under sterile conditions from the salivary glands of irradiated mosquitos. These damaged sporozoites are trapped in the sporozoite state and unable to progress in their life cycle and cause disease. The paper reports that i/v inoculation with the attenuated sporozoites protected 6/6 people who received 5 intravenous doses. None of these 6 individuals developed malaria, compared with 5/6 individuals in a control group. Despite the small study group size and the preliminary nature of these results, the study generated much excitement.
If the vaccine works as promised, it would be an extraordinary scientific milestone: the first highly effective vaccine against a parasite. Washington Post
Those numbers are tiny. But 100% protection is the best result yet in the long and frustrating effort to develop a malaria vaccine Science Magazine
I find it interesting that although several other approaches to anti-malaria vaccine development have focused on recombinant techniques, this study hearkens back to earlier vaccination approaches using attenuated, whole organisms. Other published reports about this study have highlighted its preliminary nature, and also discuss difficulties that remain to be overcome due to the labor intensive methods required to harvest sporozoites from the mosquito salivary glands and the difficulties presented by a vaccine that requires multiple i/v inoculations. The authors also stress that this is a promising start, but there is still a lot of work and more testing to be done to make an effective anti-malarial vaccine a reality. This may be a small study, bringing a glimmer of hope wrapped in cautious optimism, but in a battle that has been waged as long as this one it is a small piece of good news that appears to be very welcome indeed.
Here is the Paper:
Seder, R.A. (2013) Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine. Science DOI: 10.1126/science.1241800