Sm-p80-based DNA vaccine provides baboons with levels of protection against Schistosoma mansoni infection comparable to those achieved by the irradiated cercarial vaccine

Abstract

To date, no vaccine is available to prevent human schistosomiasis. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy, and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In the present study, we report that, in a vector approved for human use (VR1020), an Sm-p80-based DNA vaccine formulation confers a 46% reduction in the worm burden in a baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 had a 28% decrease in egg production after challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust immune responses to specific antigen Sm-p80, including immunoglobulin (Ig) G, its subtypes IgG1 and IgG2, and IgA and IgM in vaccinated animals. When stimulated in vitro with recombinant Sm-p80, peripheral blood mononuclear cells and splenocytes from baboons vaccinated with Sm-p80-VR1020 produced considerably higher levels of T helper 1 response-enhancing cytokines (interleukin [IL]-2 and interferon-gamma) than T helper 2 (Th2) response-enhancing cytokines (IL-4 and IL-10). Peripheral blood mononuclear cells produced a significantly higher number of spot-forming units for interferon-gamma than for IL-4 in enzyme-linked immunosorbent spot assays. A mixed T helper 1/T helper 2 type of humoral and T cell responses was generated after immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.

Figure 1

Protein expression of Sm-p80 in COS-7 and in CHO K1 cells. Western blot of Sm-p80 obtained following transient transfection of the DNA construct, Sm-p80-VR1020, in COS-7 cells (lane A) and CHO K1 cells (lane B). This Sm-p80-VR1020 construct was used in the vaccination experiments.

Figure 2

Adult worm burden distribution (A) and egg load per gram of liver and intestine of individual baboons (B) for groups of animals immunized with control plasmids, VR1020 (n =6) and with Sm-p80-VR1020 (n =6). Both reduction in worm burden (*P< 0.005) and in egg counts (*P< 0.05) were statistically lower in vaccinated animals.

Figure 2

Adult worm burden distribution (A) and egg load per gram of liver and intestine of individual baboons (B) for groups of animals immunized with control plasmids, VR1020 (n =6) and with Sm-p80-VR1020 (n =6). Both reduction in worm burden (*P< 0.005) and in egg counts (*P< 0.05) were statistically lower in vaccinated animals.

Figure 3

Titers of anti-Sm-p80 antibodies in immunized baboons. ELISA was performed with sera from each baboon (every four weeks) in their respective groups (VR1020 and Sm-p80-VR1020). Total IgG (A), IgG1 (B), IgG2 (C), IgA (D) and IgM (E) in individual control (JE37, WE62, TR16, JO12 and MA12) and vaccinated (MO34, RO34, LO27, CH40, BA33, and PR57) baboon sera collected every 4 weeks. The values represent the mean of three experiments ± standard error.

Figure 3

Titers of anti-Sm-p80 antibodies in immunized baboons. ELISA was performed with sera from each baboon (every four weeks) in their respective groups (VR1020 and Sm-p80-VR1020). Total IgG (A), IgG1 (B), IgG2 (C), IgA (D) and IgM (E) in individual control (JE37, WE62, TR16, JO12 and MA12) and vaccinated (MO34, RO34, LO27, CH40, BA33, and PR57) baboon sera collected every 4 weeks. The values represent the mean of three experiments ± standard error.

Figure 3

Titers of anti-Sm-p80 antibodies in immunized baboons. ELISA was performed with sera from each baboon (every four weeks) in their respective groups (VR1020 and Sm-p80-VR1020). Total IgG (A), IgG1 (B), IgG2 (C), IgA (D) and IgM (E) in individual control (JE37, WE62, TR16, JO12 and MA12) and vaccinated (MO34, RO34, LO27, CH40, BA33, and PR57) baboon sera collected every 4 weeks. The values represent the mean of three experiments ± standard error.

Figure 3

Titers of anti-Sm-p80 antibodies in immunized baboons. ELISA was performed with sera from each baboon (every four weeks) in their respective groups (VR1020 and Sm-p80-VR1020). Total IgG (A), IgG1 (B), IgG2 (C), IgA (D) and IgM (E) in individual control (JE37, WE62, TR16, JO12 and MA12) and vaccinated (MO34, RO34, LO27, CH40, BA33, and PR57) baboon sera collected every 4 weeks. The values represent the mean of three experiments ± standard error.

Figure 3

Titers of anti-Sm-p80 antibodies in immunized baboons. ELISA was performed with sera from each baboon (every four weeks) in their respective groups (VR1020 and Sm-p80-VR1020). Total IgG (A), IgG1 (B), IgG2 (C), IgA (D) and IgM (E) in individual control (JE37, WE62, TR16, JO12 and MA12) and vaccinated (MO34, RO34, LO27, CH40, BA33, and PR57) baboon sera collected every 4 weeks. The values represent the mean of three experiments ± standard error.