Immunogenicity of the Hookworm Na-ASP-2 Vaccine Candidate: Characterization of Humoral and Cellular Responses after Vaccination in the Sprague Dawley Rat

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.

Immune response studies with Wuchereria bancrofti vespid allergen homologue (WbVAH) in human lymphatic filariasis

“…ASP was initially identified from A. caninum as a major secretory protein important for its parasitism (Hawdon et al 1996). Subsequently, its homologues from different parasites such as A. ceylanicum (Goud et al 2004), O. voluvus (MacDonald et al 2004, N. americanum (Fujiwara et al 2005), and B. malayi (Murray et al 2001) were cloned and studied in detail. Apart from its protective capability, ASP from O. volvulus has been shown to induce angiogenesis when injected in the cornea of mice (Tawe et al 2000).…”

Heligmosomoides polygyrus Venom Allergen-like Protein-4 (HpVAL-4) is a sterol binding protein

“…Due to their immunomodulatory properties, ES products from H. polygyrus have been explored as putative therapeutic agents for autoimmune and allergic diseases ( Harris et al, 2014 ). Similarly, ES products have been studied as candidate vaccine antigens for hookworm infection and schistosomiasis ( Verjovski-Almeida et al, 2003 , Bethony et al, 2005 , Fujiwara et al, 2005 ).…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…Furthermore, the sera obtained from the immunized dogs significantly inhibited the migration of L3 through tissue in vitro compared to sera from control dogs, suggesting that antibodies might play a critical role in protection by decreasing the number of L3 that reach the gastrointestinal tract ( 204 ). Rats immunized with Na-ASP-2 formulated with Alhydrogel also induced strong antibody response (IgG1, IgG2a, and IgM) and induced a Th2 skewed immune response ( 215 , 216 ). However, after offering so much promise, the rNa-ASP-2/Alhydrogel vaccine was halted in 2008, having reached Phase I clinical trials, due to generalized urticarial reactions characterized by a high prevalence of IgE antibodies to larval antigens in individuals previously infected with or exposed to N. americanus in endemic populations ( 202 , 203 , 210 ).…”