Development of a Subunit Vaccine Against Babesiosis Caused by Babesia microti
Abstract
In the United States, most cases of human babesiosis are caused by Babesia microti and are acquired from the bite of an infected deer tick. Babesia microti is a small parasite that invades, multiplies inside, and eventually bursts red blood cells open, causing anemia. As the infection progresses, patients typically experience fever, chills, sweats, headache, myalgia, and anorexia. In individuals older than 50 years, babesiosis can be so severe that hospital admission is warranted. Despite antimicrobial therapy, lung inflammation and/or loss of kidney function can develop and be fatal. The number of cases reported each year to health authorities has increased 10-fold in the past two decades. Current measures to prevent babesiosis aim at reducing tick exposure and removing ticks embedded in the skin. The proposed research aims at developing a subunit vaccine against babesiosis caused by B. microti. As such, it responds to a Fiscal Year 2022 Tick-Borne Disease Research Program Focus Area outlined for Prevention. Our vaccine strategy is to trigger an antibody response that will interrupt the lifecycle of Babesia microti in the vaccinated host. To identify Babesia microti proteins against which an infected host develops a strong antibody response, we screened the entire set of proteins produced by the parasite. Using a strain of laboratory mice that relies on antibodies to resolve Babesia microti infection, we discovered that these antibodies recognize a small set of parasite proteins. We probed for functional evidence that neutralization of those proteins drives resolution of infection. In doing so, we identified three parasite proteins that are well suited for use in a subunit vaccine. We propose to identify vaccine compositions that confer full protection to young and old mice from B. microti. We will produce the three prioritized proteins and verify that these proteins are recognized by antibodies made during the course of B. microti infection in mice and in humans. Each vaccine composition will comprise one of the three proteins mixed with one of two adjuvants, compounds that promote antibody production. One adjuvant is used in seasonal flu vaccines for the elderly. The other adjuvant strengthens vaccine-induced immunity against a parasite that causes malaria. We will immunize mice of a strain in which old age exacerbates the burden of B. microti but will initiate our studies by seeking to reveal protection in young age. Anticipating that protection conferred by immunization with a single protein will be partial, we will combine two or three of the prioritized proteins as long as they each confer partial protection and will seek to identify a combination that confers full protection to young mice. We will assess whether this combination confers equal protection to old mice. If not, we will vary the adjuvant and/or the dose or frequency of protein. We will assess whether vaccine compositions that confer protection from the life stage of B. microti that causes disease in the host (the vaccine target) also confer protection from the life stage of B. microti that is delivered in the skin by an embedded tick and quickly progresses to the life stage that causes disease. Aside from being life-threatening, severe babesiosis can be difficult and costly to treat. Veterans who are beyond 50 years of age will benefit the most from a vaccine against babesiosis because they are at highest risk of severe illness. Active-duty Service Members, despite a low risk for severe babesiosis due to their young age, will benefit from a vaccine against babesiosis because they will escape symptoms. By reducing the duration of B. microti infection in asymptomatic carriers who may donate blood, a vaccine will protect the blood supply, thereby benefiting any military Service Member in need of a blood transfusion. These considerations extend to military beneficiaries as well as the general population. The proposed resea
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310677
Entities
People
- Edouard Vannier
Organizations
- Tufts Medical Center
- United States Army