Breastfeeding is a major route of vertical HIV transmission. Many methods have been proposed to prevent milk-borne HIV infection, including anti-retroviral therapy, wet nursing by an HIV-negative woman, formula feeding, replacing mother's milk with modified animal milk, treating mother's milk with Holder pasteurization, lipolysis, or microbicides, and obtaining human milk from an uninfected/treated milk bank. Probably due to high cost, obtrusiveness, inaccessibility, and/or inconvenience, none of these methods has been widely accepted and practiced by most HIV-infected mothers in HIV- prevalent developing countries. To block milk-borne HIV transmission from mothers to infants, therefore, a more practical prophylaxis is urgently needed. We have developed a probiotic approach to inactivate HIV with commensal lactobacilli. These lactobacilli were specifically selected for their ability to capture HIV with mannose-binding lectin (MBL). Because HIV virions and infected cells are coated by mannose-rich glycoproteins, these lactobacilli can block both cell-free and cell-associated HIV. Our long-term goal is to develop a bio-prophylaxis based upon MBL+ lactobacilli. These bacteria can be delivered orally to infants for blocking HIV from mother's milk, but the bacteria ideally should be maintained viable with a long shelf life in a proper formula and package. The formula must also be tested safe in animals. This SBIR phase I project will focus on formulation and safety. We hypothesize that once hydrated, lactobacilli from a freeze-dried powder formula are as effective as fresh bacteria in capturing HIV and are safe to animals.
The Specific Aims are to: 1) optimize formulation, packaging, and shelf life of the infant probiotic prophylaxis formula, and 2) study safety and survival of virus-capturing lactobacilli in rats. The proposed studies will produce a prototype probiotic formula and obtain important preclinical data regarding the virus-trapping lactobacilli, which will guide future in vivo studies in primates and in humans. Ultimately, our probiotic approach may offer a safe, unobtrusive, cost-effective and convenient prophylaxis for blocking milk-borne HIV transmission in infants. Breastfeeding contributes a large number of mother-to-child HIV transmission. Although physical barriers have been used to effectively blocking HIV transmission from men to women, no effective or practical methods are yet available to block milk-borne HIV transmission from mothers to infants. Therefore, a more practical prophylaxis is urgently needed. We have developed a probiotic approach to inactivate HIV with commensal lactobacilli. These lactobacilli were specifically selected for their ability to capture HIV by binding to the viral mannose-rich glycoproteins. The proposed study is to develop a probiotic formula based on these bacteria for oral delivery to infants for blocking HIV from mother's milk. Appropriate formulation will be studied to test for shelf life and safety in animals as the phase I SBIR project. A major milestone will be the production of a prototype probiotic formula. Our long-term goal is to develop a safe, unobtrusive, cost-effective and convenient prophylaxis for blocking milk-borne HIV transmission in infants. ? ? ?
