Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum.
ABSTRACT Syrian Golden hamsters were vaccinated with the recombinant fusion proteins Ay-ASP-2 and Ay-MTP-1 from the infective larvae of the hookworm Ancylostoma ceylanicum. Vaccines comprised each antigen alone or the combination of the two proteins. All vaccinated group developed high antibody titers (>1:40,000); coadministration of a second antigen did not significantly affect the magnitude of the antibody response. Following challenge, hamsters vaccinated with each single antigen exhibited reductions in worm burden (32% and 28% to Ay-ASP-2 and Ay-MTP-1, respectively) and fecal egg counts (56% and 43%, respectively). A vaccine cocktail, containing both antigens further reduced worm burden (36%) and fecal egg counts (59%) (p<0.001). Moreover, vaccination with the antigen cocktail significantly improved hemoglobin values (p=0.01) and body weights (p=0.001) compared to what achieved with either each antigen or adjuvant alone. Taken together, these data suggest that combination of two or more antigens may present an effective vaccine development strategy to improve protection and/or disease symptoms in affected individuals.
Article: Reduction of worm fecundity and canine host blood loss mediates protection against hookworm infection elicited by vaccination with recombinant Ac-16.[show abstract] [hide abstract]
ABSTRACT: Hookworm infection is one of most important parasitic infection of humans, occurring in 740 million people. Here we report the protective vaccination of dogs with Ac-16, an immunodominant surface antigen from the hookworm Ancylostoma caninum. We show that immunization with Ac-16 formulated with AS03 elicited specific humoral and cellular immune responses and provided partial protection against hookworm infection and morbidity as evidenced by a significant reduction of hookworm egg counts (64% reduction; P = 0.0078) and worm-induced blood loss (P < 0.05). Moreover, specific anti-Ac-16 antibodies recognized the native protein on the surface of third-stage larvae and blocked their migration through tissue in vitro. Our data support the use of Ac-16 as a potential candidate for vaccination against hookworm infection.Clinical and Vaccine Immunology 03/2007; 14(3):281-7. · 2.55 Impact Factor
Article: Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat.[show abstract] [hide abstract]
ABSTRACT: The recombinant larval protein Na-ASP-2 from the human helminth parasite Necator americanus is a lead candidate for a human hookworm vaccine. We have characterized the humoral and cellular immune responses elicited by the Na-ASP-2 formulated with the aluminum-based adjuvant Alhydrogel in the Sprague Dawley rat. We demonstrated that Na-ASP-2 vaccine induced a strong antibody response at all doses tested, as evidenced by high specific IgG1, IgG2a and IgM titers. High IgG antibody titers were maintained up to three months post vaccination and were boosted by an additional vaccine dose. Specific cell proliferation and a Th2 cytokine profile were also observed in peripheral blood of all rats immunized with the formulated vaccine. Host IL-6 levels were also significantly elevated. These data provide evidence that the immune response of the Na-ASP-2 vaccine is robust and durable and therefore suitable for the further clinical development of the Na-ASP-2 vaccine.Human vaccines 1(3):123-8. · 3.58 Impact Factor