Longevity of Sm-p80-specific antibody responses following vaccination with Sm-p80 vaccine in mice and baboons and transplacental transfer of Sm-p80-specific antibodies in a baboon

Abstract

Based on data obtained using vaccine efficacy studies in mice, hamsters, and baboons, the credentials of Sm-p80 as a first tier vaccine candidate for schistosomiasis have been well established. Sm-p80-based vaccine formulation(s) have consistently exhibited potent prophylactic efficacy in reducing adult worm burden following cercarial challenge and induce killing of established adult worms in chronic infection. This vaccine is protective against both intestinal and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific antibody responses was studied in mice and in baboons. Robust antibody titers were detected in mice for up to 60 weeks following vaccination with Sm-p80 recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon, transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in the baby. These long-lasting humoral immune response data coupled with the vaccine efficacy data in rodents and nonhuman primates further strengthens the case for Sm-p80 to be moved forward through development leading to human clinical trials.

Fig. 1

Sm-p80 specific antibody titers in the sera obtained from mice immunized with Sm-p80 protein with GLA-SE and boosted twice and then challenged with cercariae after 4 weeks of the last injection. Groups 1 and 2 were inoculated three times with GLA-SE or Sm-p80 plus GLA-SE. Titers of IgG, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA are shown in panels a–g. Consistently higher levels of antibody titers were observed in the group immunized with Sm-p80 plus GLA-SE compared to adjuvant control group. All of the values represent as mean of triplicate experiments±standard deviation

Fig. 2

Sm-p80 specific antibody titers in the sera obtained from mice immunized with Sm-p80 protein with GLA-SE and boosted once and then challenged with cercariae after 4 weeks of the last injection. Groups 3 and 4 were inoculated two times with GLA-SE or Sm-p80 plus GLA-SE. Titers of IgG, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA are shown in panels a–g. Consistently higher levels of antibody titers were observed in the group immunized with Sm-p80 plus GLA-SE compared to adjuvant control group. All of the values represent as mean of triplicate experiments±standard deviation

Fig. 3

Sm-p80 specific antibody titers in the sera obtained from mice immunized with Sm-p80 protein with GLA-SE and boosted once and then challenged with cercariae after 10 weeks of the last injection. Groups 5 and 6 were inoculated two times with GLA-SE or Sm-p80 plus GLA-SE. Titers of IgG, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA are shown in panels a–g. Consistently higher levels of antibody titers were observed in the group immunized with Sm-p80 plus GLA-SE compared to adjuvant control group. All of the values represent as mean of triplicate experiments±standard deviation

Fig. 4

Sm-p80 specific antibody titers in the sera obtained from mice immunized with Sm-p80 protein with GLA-SE and boosted once and then challenged with cercariae after 16 weeks of the last injection. Groups 7 and 8 were inoculated two times with GLA-SE or Sm-p80 plus GLA-SE. Titers of IgG, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA are shown in panels a–g. Consistently higher levels of antibody titers were observed in the group immunized with Sm-p80 plus GLA-SE compared to adjuvant control group. All of the values represent as mean of triplicate experiments ± standard deviation

Fig. 5

Longevity of Sm-p80 specific antibody titers in sera obtained from mice immunized with Sm-p80 protein with GLA-SE over 60 weeks. Groups 9 and 10 were inoculated two times with GLA-SE or Sm-p80 plus GLA-SE. Titers of IgG, IgG1, IgG2a, IgG2b, IgG3, IgM, and IgA are shown in panels a–g. Consistently higher levels of antibody titers were observed up to 60 weeks in mice immunized with Sm-p80 plus GLA-SE compared to the adjuvant control group in which specific antibodies were nearly undetectable. All of the values represent as mean of triplicate experiments±standard deviation

Fig 6

a Sm-p80-specific IgG titers in the sera of baboons after 5 to 8 year post-vaccination. Three baboons were followed for Sm-p80 specific antibodies after Sm-p80-DNA vaccine immunization. For details of immunization schedule and associated antibody responses following vaccination with Sm-p80-based DNA vaccine, please see Siddiqui et al. 2005, Vaccine 23:1451–1456 (Siddiqui et al. 2005). Baboon ID# 421F5 was injected with 500 μg Sm-p80-pcDNA3, and the two (ID# 42275 and ID# 42285) were injected with 500 μg Sm-p80-pcDNA3 plus 500 μg pORF-hIL-2. All of the baboons received primary immunization and three boosters of the vaccine at monthly intervals. b Transplacental transfer of Sm-p80 specific antibody following vaccination of baboon mother with a Sm-p80-based DNA vaccine. One pregnant baboon was inadvertently used in the vaccine efficacy study using Sm-p80-VR1020 which has been published previously (Zhang et al. 2010, Journal of Infectious Diseases 201: 1105–1112) (Zhang et al. 2010). Following immunizations, the baby was delivered and umbilical cord blood was collected (24 week gestation); blood was also collected when the baby was 6 months old. Sera from these samples were analyzed for Sm-p80-specific IgG titer