The Borrelia burgdorferi outer surface membrane proteins BBA65, BBA66, BBA69, BBA70, and BBA73 were tested for their ability to confer protection against B. burgdorferi infection challenge. Mice were immunized with recombinant forms of the proteins singly or in combinations. Following initial protein inoculation and booster injections, seroconversion was confirmed prior to B. burgdorferi challenge by tick bite. Despite mice having high antibody titers for each antigen, no significant protections against the challenge infections were observed. These results demonstrate that these recombinant proteins were not protective and reflects the challenges confronted to identify effective novel vaccine candidates for Lyme disease.