Virus-based vaccines show promise for malaria prevention

Researchers based at the Department of Molecular Microbiology and Immunology at the Hopkins Bloomberg School of Public Health have been developing a malaria vaccine based on a non-pathogenic and non-vertebrate insect virus, or “baculovirus.” These are promising new alternatives to current malaria multi-stage vaccines.

Malaria cases are caused by transmission of a parasite via a mosquito bite, the most lethal form of which is P. falciparum. The malaria parasite, which is located in a mosquito’s mid-gut, can be stopped by antibodies that are directed at antigens at the parasite’s surface. These antibodies reduce or limit transmission of the parasite, and are synthesized by the body in response to the presentation of the antigen. This concept is known as a transmission-blocking vaccine, an idea that the researchers employed for their study.

Godfree Mlambo, of the Hopkins Bloomberg School of Public Health, was one of the authors of the study. The study involved generating recombinant, or genetically modified, baculovirus that displayed a transmission-blocking vaccine candidate called Pfs25.

This new vaccine vector is attractive for several reasons. It has low toxicity in the body, it cannot replicate in mammalian cells, and it is free of pre-existing antibodies, which eliminates any extraneous immune system responses.

Baculovirus particles expressing Pfs25 on the surface were discovered in the laboratory. The study showed that mice immunized with this baculovirus produced high levels of antibodies specific to Pfs25. These results, which were similar for intranasal and intramuscular immunizations, showed the potential effectiveness of vaccines in the form of whole virus particles, even through an intranasal route.

Due to safety concerns and discomfort associated with needles, intranasal or oral immunization is an attractive option, even for diseases that are not transmitted nasally. In fact, the baculovirus, when administered intranasally, was shown to have the additional benefit of protecting mice from a lethal dose of influenza.

Mlambo’s co-author, Nirbhay Kumar of the Bloomberg School of Public Health and the Tulane University School of Public Health & Tropical Medicine, explained, “The main goal of our research is to develop a vaccine to stop transmission of human malaria.” The parasites transmitted by female anopheline mosquitoes annually infect more than 500 million people worldwide, two million of which are children.

In previous cases, the baculovirus has been effective as a vaccine target, but proper delivery has been an issue. In addition, the researchers have been involved in testing the functional outcomes of giving vaccinations. This latest research takes into account such previous studies, as well as the mouse model for testing human malaria transmission, marking a step forward in malaria research.

Although more work remains to be done, the researchers are optimistic about their findings. “If successful,” Kumar said, “this type of vaccine could play a significant role in contributing towards the gradual elimination of malaria in different regions of the world . . . [and] induce an effective immunity to this parasitic disease.”