Insight: Research Edition

Fall 2005

Researcher Has Vision of Pan-Arthropod Vaccine

Despite its best efforts during the last 50 years, the World Health Organization has not been able to realize its dreams of vaccinations against some of humankinds’ most ancient and devastating diseases including malaria, yellow fever, dengue fever, plague, Rift Valley fever and other arthropod-borne infectious diseases. A research team at Colorado State University is hoping that its work will one day help WHO make its dream come true.

A novel idea, which has taken more than a decade to achieve scientific acceptance, focuses on creating a vaccine not against the pathogens that cause disease, but against the saliva in the arthropods that transmit the pathogens – saliva that researchers now believe is critically important to the successful transmission of disease.

The laboratory of Dr. Richard Titus, a Professor in the Department of Microbiology, Immunology and Pathology, along with research partners in the College’s Arthropod-Borne and Infectious Disease Laboratory (AIDL), and with other international research efforts, has been instrumental in understanding how saliva in arthropods creates ideal conditions in the vertebrate host when pathogens, for example Leishmania, are introduced into the host when the arthropod takes a blood meal.

“When sand flies inject Leishmania into the vertebrate host, they inject the parasite within their saliva,” said Dr. Titus. “Sand fly saliva contains many proteins which help the fly obtain a blood meal. In addition, the saliva contains potent immunosuppressive proteins which can be critical to survival of the parasite within the host. We are looking at an alternative approach for vaccinating against Leishmania that involves developing vaccines against salivary proteins in an attempt to block the action of these proteins when the fly bites and thus prevent infection with Leishmania.”

Dr. Titus first became involved with salivary studies when he was at Harvard Medical School. A colleague, Dr. José Ribeiro, was interested in sand flies and Dr. Titus was interested in leishmaniasis. Dr. Ribeiro was investigating the pharmacological properties of the sand fly’s saliva, while Dr. Titus was curious as to how the sand fly transmitted disease. Later on, Dr. Titus became aware of the work of Dr. Peter Willadsen of Australia who devised a new way of protecting cattle from ticks. Rather than vaccinating against the tick, Dr. Willadsen created a vaccine that immunized the cow against a component of the tick’s digestive track – a protein called Bm86. When vaccinated, cows develop antibodies to the protein so when a tick feeds, the tick gets a bad case of indigestion since the cow’s blood basically attacks the tick’s intestines.

“Dr. Willadsen was really thinking outside the box and it got me thinking outside the box, too,” said Dr. Titus.

Arthropods, which include mosquitoes, sand flies, ticks, black flies and biting midges, transmit some of the most devastating and deadly diseases in the world. If researchers are successful in identifying a common protein denominator in saliva that has been preserved across evolutionary time in the different species of arthropods, they may be able to develop a single vaccine that would provide protection against all diseases transmitted by arthropods – a pan-arthropod vaccine. Dr. Titus concedes that the possibility of such a vaccine is in the distant future, but it is an enticing goal to work toward.

“We have a beautiful model here at CSU of how important saliva is to disease transmission,” said Dr. Titus. “Dr. Barry Beaty and his group at AIDL have done fascinating work that shows how transmission of the LaCrosse virus is enhanced by the presence of saliva from the host mosquito. Using this as our model, and with increased funding and facilities from the Regional Center of Excellence, we hope to make rapid progress.”Dr. Beaty’s research showed that when adult mice were injected with the LaCrosse virus alone, they did not develop disease. When they were injected with the virus accompanied by saliva, as would occur through normal infection through the mosquito host, the mice died.

“It’s an amazingly clean finding with no shades of gray,” said Dr. Titus. “With just the virus, the mice lived – with the virus and saliva, the mice died. If we can immunize against one component of the saliva that modifies the immune system, we may be able to offer protection against infection.”

Dr. Titus’ work has implications for a diverse set of concerns. First and foremost, because of the RCE’s objectives for biodefense, he is working to develop vaccines that offer protection to targeted populations in case of attack by a biological weapon. His work also has implications for military personnel who are increasingly deployed in areas where they have little natural immunity to regional diseases, such as leishmaniasis, which soldiers stationed in Afghanistan and Iraq are contracting in increasing numbers. Third, emerging infectious diseases are posing a greater threat to global populations with little available in terms of vaccines, therapeutics and diagnostics. Fourth, and perhaps most important, a viable vaccine against arthropod-borne diseases would alleviate unbelievable levels of suffering and change the course of human history.

“We don’t expect that our work will provide the complete answer, but it is part of a new way of thinking about how to protect against these diseases,” said Dr. Titus. “Our discoveries might become one component of a comprehensive vaccine to prevent infection. But this type of thinking represents a huge shift in how we approach infectious disease and it’s very rewarding to be a part of that.”