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. Author manuscript; available in PMC: 2021 Nov 15.
Published in final edited form as: Parasitol Res. 2014 Apr 12;113(6):2239–2250. doi: 10.1007/s00436-014-3879-8

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

Weidong Zhang 1,2, Gul Ahmad 3, Loc Le 4,5, Juan U Rojo 4,5, Souvik Karmakar 4,5, Kory A Tillery 4,5, Workineh Torben 6, Raymond T Damian 7, Roman F Wolf 8, Gary L White 8, David W Carey 8, Darrick Carter 9,10, Steven G Reed 11, Afzal A Siddiqui 12,13,14,15
PMCID: PMC8592056  NIHMSID: NIHMS1751593  PMID: 24728521

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.

Keywords: Schistosomiasis, Schistosoma, Sm-p80, Calpain, Prophylactic vaccine, Nonhuman primate, Baboon, Transplacental antibodies transfer, Longevity of antibody responses

Introduction

Estimates of the burden of schistosomiasis currently stands at 200–400 million people infected in 74 countries with steadily increasing detrimental effects on infected individuals as determined by health-related quality of life. This is further exacerbated by the fact that an additional three quarters of a billion people are at risk of acquiring the infection (Beaumier et al. 2013; Hotez and Kamath 2009; Jenkins-Holick and Kaul 2013; Rollinson et al. 2013; Terer et al. 2013). Schistosomiasis is gaining footholds in previously clear geographical areas despite significant efforts to eradicate the intermediate snail host; investment in better-quality public health infrastructure; and implementation of initiatives based on Mass Drug Administration (MDA) using praziquantel (King 2010; Parker and Allen 2011; Prichard et al. 2012; Rollinson et al. 2013). The emerging consensus among the experts in the field is that for durable and long-lasting schistosomiasis control, adding a vaccine to existing control measures would be greatly beneficial in reducing the overall burden of the disease (Bergquist et al. 2002, 2005; McManus and Loukas 2008; Mo et al. 2014). Currently, no approved vaccine is available for human use to prevent or treat schistosomiasis. Efficacy data from rodent and nonhuman primate models clearly indicate that Sm-p80-based vaccines consistently exhibit protection from infectious cercariae and also help in killing of adult worms in established, chronic infections (Ahmad et al. 2009b, 2011; Karmakar et al. 2014b; Zhang et al. 2010). In addition, Sm-p80-based vaccines markedly reduce the egg-induced pathology; this can aid in gradually reducing the transmission rates. Finally, these vaccines have shown effectiveness against both intestinal and urinary schistosomiasis (Ahmad et al. 2009b, 2011; Karmakar et al. 2014a, b; Zhang et al. 2010).

An important component which plays an essential role in establishing the eventual effectiveness of a vaccine is the generation of robust, sustainable, and long-lasting protective immune responses (Komegae et al. 2013a; Clark et al. 2012; Vujanic et al. 2012; Elgueta et al. 2010). Therefore, in the present study, we have demonstrated strong antibody responses to Sm-p80 in mice for up to 60 weeks following vaccination with a recombinant vaccine formulation (Sm-p80+GLA-SE). Furthermore, we have followed up three baboons for 5 to 8 years after the initial vaccination with an Sm-p80-based plasmid DNA vaccine (Sm-p80-pcDNA and Sm-p80-pcDNA+pORF-hIL-2) (Siddiqui et al. 2005), sera from these baboons exhibited appreciable Sm-p80-specific IgG titers. Homologous and heterologous transfer of Sm-p80-specific purified IgG has demonstrated that these antibodies are meaningful for protection (Torben et al. 2011, 2012). In addition, during the course of the vaccine efficacy trial using the Sm-p80-DNA vaccine (Sm-p80-VR 1020) in baboons (Zhang et al. 2010), one pregnant baboon was inadvertently vaccinated. In this baboon, Sm-p80-specific IgG titers were detected in the serum obtained from the vaccinated mother, umbilical cord blood, and the 6-month-old baboon baby. This transplacental transfer of Sm-p80-specific IgG is a significant finding, but should be interpreted with caution because it was measured in only one animal; however, performing such studies with larger sample size of nonhuman primates would be difficult to justify without a sound basis which this observation provides. Overall, the studies in this work indicate durable and prolonged longevity of Sm-p80-specific humoral responses following vaccination with Sm-p80-based vaccines in both rodents and nonhuman primates.

Materials and methods

Animals and parasites

Biomphalaria glabrata snails infected with Schistosoma mansoni (NMRI strain) were obtained from the NIAID Schistosomiasis Resource Center, Biomedical Research Institute, Rockville, MD, USA. Female C57BL/6 mice were purchased from Charles River Laboratories International Inc. (Wilmington, MA, USA). Details of nonhuman primates have been published previously (Siddiqui et al. 2005; Zhang et al. 2010). Briefly, baboons (Papio anubis) were obtained from the University of Oklahoma Health Sciences Center (OUHSC) baboon breeding colony and housed in AAALAC accredited facilities at OUHSC. Baboons were pre-screened for intestinal and blood parasites and for antibodies that were cross-reactive to Sm-p80 and were found negative for both. The use of mice and baboons in this study was approved by the Institutional Animal Care and Use Committees of TTUHSC and OUHSC, respectively.

Preparation of vaccine formulations and immunization protocol

The details of protein (recombinant Sm-p80) and DNA immunogen preparations have been published previously (Ahmad et al. 2009a, 2011; Karmakar et al. 2014a; Zhang et al. 2010). A total of 130 mice were divided into control and experimental groups: each mouse in the experimental group received 25 μg protein vaccine (rSm-p80) with 5 μg GLA-SE by intramuscular injection at the time points outlined in Table 1, while each mouse in the control group received solely 5 μg GLA-SE by intramuscular injection. The dosage of the protein antigen used was based on our previous published studies in which the vaccine regimen was optimized (Ahmad et al. 2009a, 2011; Karmakar et al. 2014a; Zhang et al. 2010) Three baboons were followed from 2008 to 2011 for Sm-p80 specific antibodies after Sm-p80-DNA vaccine immunization completed in 2003 (Siddiqui et al. 2005). For details of the immunization schedule for baboons and associated antibody responses following vaccination with Sm-p80-based DNA vaccine, please see Siddiqui et al. (Siddiqui et al. 2005). In addition, one pregnant baboon was unintentionally utilized in the vaccine study in 2008–2009; please see Zhang et al. (Zhang et al. 2010) for immunization protocol and associated antibody responses.

Table 1.

Details of the schedule used to vaccinate C57BL/6 mice with Sm-p80 vaccine (immunization, blood collection, challenge, and necropsy schedule)

Group number n Week 0 Week 4 Week 8 Week 12 Week 14 Week 18 Week 20 Week 26
Group 1 15 5 μg GLA-SE 5 μg GLA-SE 5 μg GLA-SE Challenge Sacrifice
Group 2 15 25 μg rSm-p80+5 μg GLA-SE 25 μg rSm-p80+5 μg GLA-SE 25 μg rSm-p80+ 5 μg GLA-SE Challenge Sacrifice
Group 3 10 5 μg GLA-SE 5 μg GLA-SE Challenge Sacrifice
Group 4 10 25 μg rSm-p80+5 μg GLA-SE 25 μg rSm-p80+5 μ GLA-SE Challenge Sacrifice
Group 5 10 5 μg GLA-SE 5 μg GLA-SE Challenge Sacrifice
Group 6 10 25 μg rSm-p80+5 μg GLA-SE 25 μg rSm-p80+5 μg GLA-SE Challenge Sacrifice
Group 7 10 5 μg GLA-SE 5 μg GLA-SE Challenge Sacrifice
Group 8 10 25 μg rSm-p80+ μg GLA-SE 25 μg rSm-p80+5 μg GLA-SE Challenge Sacrifice
Group 9 20 5 μg GLA-SE 5 μg GLA-SE
Group 10 20 25 μg rSm-p80+5 μg GLA-SE 25 μg rSm-p80+5 μg GLA-SE
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Animals from groups 9 and 10 were bled at 2–4 week intervals until 60 weeks

Parasite challenge and worm burden determination

Mice from each group were challenged with 150 cercariae of S. mansoni at various weeks after vaccination and sacrificed 6 weeks after challenge. Necropsies and determination of protection were carried out as previously described (Ahmad et al. 2009b). Briefly, adult worms were perfused from the hepatic portal system and manually removed from the mesenteric veins. Protection (P) was calculated by comparing worm burdens from immunized (I) and control (C) mice by a standard formula: %P=[(C−I)/C×100].

Enzyme-linked immunosorbent assays for the detection of antibodies in mice

Serum samples from each mouse were collected at the interval of 2 or 4 weeks. For the study of long-term duration of antibody response (group 9 and group 10), mice were bled at select intervals (generally per month) until 60 weeks. Antibody titers for total IgG, IgG subtypes (IgG1, IgG2a, IgG2b, and IgG3), IgM, and IgA were measured using the pooled sera from each time point of control and experimental group as described previously (Ahmad et al. 2009b). All of the samples were assayed in triplicate. The curve of antibody titer was plotted against time and expressed as the mean±SD.

Enzyme-linked immunosorbent assays for antibody longevity and transplacental study in baboons

Three baboons were utilized after DNA vaccine immunization in 2003 (Siddiqui et al. 2005). Baboon sera collection continued after 5 years followed by several intervals up to 8 years. Total IgG antibody titers were determined by ELISA as described previously (Ahmad et al. 2009a; Karmakar et al. 2014a, b; Siddiqui et al. 2005; Zhang et al. 2010). In a separate study carried out in 2008–2009, a pregnant baboon (ID# CH40) was unknowingly used in Sm-p80-VR1020 immunized group (Zhang et al. 2010). The baboon baby (ID# 2304) was born after mother (ID# CH40) received the third boost and umbilical cord blood was collected. In addition, 6 months after the baby was born; sera were collected and analyzed for IgG titer.

Statistical analysis

Single and multiple parameters were evaluated by unpaired t test and two-way ANOVA within groups using GraphPad Prism 5.04. P values obtained by these methods were considered significant if they were ≤0.05.

Results

Reduction in worm burden

Table 2 show that Sm-p80 in combination with the TLR4 ligand based adjuvant, GLA-SE, gives significant reduction in worm burden in vaccinated animals as compared with the respective control groups, which received only the GLA-SE adjuvant. Groups 1 and 2 were boosted twice and gave the highest worm reduction (42 %). The groups 3 and 4, groups 5 and 6, or groups 7 and 8 were boosted once and showed 36, 32, and 15 % reduction in worm burden, respectively.

Table 2.

Protection data obtained from C57BL/6 mice vaccinated with Sm-p80 vaccine

Group number Total number of worms Worm burden (mean±SE) Worm burden for group (mean±SE) % Reduction in worm burden
Expt1 n Expt2 n Total Expt1 Expt2
Group 1 193 7 226 8 419 27.57±2.82 29.14±2.31 27.93±1.74
Group 2 102 7 142 8 244 14.57±1.60 17.75±1.78 16.27±1.24 41.77*
Group 3 103 5 91 5 194 20.60±2.54 18.20±1.66 19.40±1.48
Group 4 67 5 58 5 125 13.40±1.12 11.60±1.86 12.50±1.07 35.57*
Group 5 117 5 132 5 249 23.40±4.45 26.40±6.03 24.90±3.57
Group 6 94 5 76 5 170 18.80±1.59 15.20±1.83 17.00±1.29 31.73*
Group 7 42 5 60 5 102 8.40±2.16 12.00±2.43 10.20±1.65
Group 8 36 5 51 5 87 7.20±2.08 10.20±1.74 8.70±1.37 14.71*
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*

p<0.05

Sm-p80 specific antibody titers in the sera obtained from mice immunized with Sm-p80 protein with GLA-SE

Serum antibody titers for total IgG, IgG subtypes (IgG1, IgG2a, IgG2b, and IgG3), IgM, and IgA were determined using ELISAs. In the case of groups 1 and 2 (immunized with GLA-SE or Sm-p80 with GLA-SE and boosted twice and then challenged with cercariae 4 weeks after the last injection), the titers for IgG, its subtypes, IgM and IgA were detectable at week 2 and peaked at week 10. The titers of IgG and IgG2b were higher with two boosts when compared to groups receiving one boost (Fig. 1). In the case of groups 3 and 4 (immunized with GLA-SE or Sm-p80 with GLA-SE and boosted once and then challenged with cercariae 4 weeks after the last injection), the titers for IgG, its subtypes, and IgM were detectable at week 2 while the IgA response was delayed until week 4; antibody responses peaked at week 6 (Fig. 2). In the case of groups 5 and 6 (immunized with GLA-SE or Sm-p80 with GLA-SE and boosted once and then challenged with cercariae 10 weeks after the last injection), total IgG, its subtypes, IgM, and IgA showed a similar pattern to groups 3 and 4 (Fig. 3). In groups 7 and 8 (immunized with GLA-SE or Sm-p80 with GLA-SE and boosted once and then challenged with cercariae 16 weeks after the last injection), the titers for total IgG, its subtypes, and IgM were detectable at week 2, yet IgA responses were delayed until week 4; antibody responses peaked at week 6 (Fig. 4). In groups 9 and 10 (immunized with GLA-SE or Sm-p80 with GLA-SE and boosted once and mice were not challenged), the titers for the total IgG, its subtypes, and IgM were detectable at week 2, while IgA rose at week 4. After 18 to 24 weeks, the titers for total IgG and its subtypes stabilized to a near constant level up to week 60. For IgA, the titer decreased from week 20, but was noticeable throughout 60 weeks. However, for IgM, after peaking at week 6 the titer diminished and was undetectable at week 56 (Fig. 5).

Fig. 1.

Fig. 1

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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.

Fig. 2

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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.

Fig. 3

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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.

Fig. 4

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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.

Fig. 5

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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

Sm-p80-specific IgG titers in the sera of baboons after 5 to 8 years post-vaccination

For the baboon ID# 421 F5 (immunized with Sm-p80-pcDNA3 in 2003), serum samples were obtained six times from 2008 to 2011. The titers for total IgG stayed between 1:400 and 1:800. For the baboon ID# 42275 and ID# 42285(immunized with Sm-p80-pcDNA3+pORF-hIL-2 in 2003), sera were collected five times from 2008 to 2010 and 2008 to 2011, respectively. The titers for total IgG in baboon ID# 42275 remained at 1:800 throughout 7 years. The titers for total IgG in baboon ID# 42285 stayed between 1:800 and 1:1,600 (Fig. 6a).

Fig 6.

Fig 6

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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

Transplacental transfer of Sm-p80 specific antibody following vaccination of baboon mother with a Sm-p80-based DNA vaccine

One pregnant baboon was unintentionally used in an Sm-p80 vaccine study. Antibody data relating to the mother, ID# CH40, were published in 2010 (Zhang et al. Journal of Infectious Diseases 201: 1105–1112) (Zhang et al. 2010). The sera samples from the umbilical cord blood and blood taken from the baby baboon 6 months after delivery were used for antibody testing by ELISA. The titer for total IgG specific to Sm-p80 from umbilical cord blood reached 1:12,800. The titer for total IgG specific to Sm-p80 from the baby decreased to 1:400 six months after birth (Fig. 6b).

Discussion

Antibody titers presented here clearly indicate that Sm-p80-based recombinant protein and DNA vaccines produce potent, long-lasting humoral responses which are correlated with protection, i.e., reduction in worm burden. During the entire duration of experimentation (60 weeks), Sm-p80-specific antibody responses were detectable in mice. Similarly, in baboons, IgG titers were discernable for the entire duration examined, i.e., 8 years. Robust titers and their trends indicate that it is possible that these responses may last throughout the life span of both mice and baboons. This is important to note that a recombinant vaccine formulation was used in mice and a naked DNA vaccine was utilized in the baboons; both of these strategies exhibited long-lasting antibody responses. We have previously shown that antibodies play an important role in Sm-p80-mediated protection both in mice and baboons (Torben et al. 2011, 2012). It may be important to perform additional immunologic assessments to obtain a broader representation of immune responses which could include T cell proliferation, cytokine secretion, and cell phenotyping, among others; all of which are important markers of Sm-p80 vaccine-mediated protection (Ahmad et al. 2009a, b, 2011; Karmakar et al. 2014a, b; Zhang et al. 2010). The durability and potency of the vaccine-mediated immune response detected in our study is comparable or better than the protective threshold known for other infectious disease pathogens ranging from virus to protozoa, as well as that known for a variety of hosts ranging from mice to humans (Clark et al. 2012; Kitphati et al. 2009; Sabarth et al. 2012; Skerry and Mahon 2011; Vujanic et al. 2012). It is important to note that to achieve ideal protective and therapeutic efficacy and adaptive immune responses using Sm-p80, the addition of TLR4-based adjuvant is extremely beneficial, as is the case in this study and as has been reported previously (Karmakar et al. 2014a, b). Properly formulated TLR agonists have been reported as powerful adjuvants, and they contribute immensely in the generation of long-lasting immune responses (Carter and Reed 2010; Ireton and Reed 2013; Reed et al. 2013; Steinhagen et al. 2011; Taillardet et al. 2010). Furthermore, the generation of long-lived antibody-secreting cells and memory B cells are critical events for an effective vaccine and the choice of adjuvant can influence these processes (Komegae et al. 2013a, b). We intend to confirm the role of memory B cells in the longevity of Sm-p80 vaccine-mediated antibody responses using clonal expansion and cell phenotyping (e.g., CD 19, CD27) in future experiments.

Transplacental transfer of IgG in baboon indicates that longevity of antibody response is not due to the long-term continual release of antigen from the plasmid DNA encoding Sm-p80. It is possible that cells that secrete antibodies at a low frequency could be involved in placental transfer and later the transfer of immune components continued through colostrum/lactation (Peroni et al. 2013; Palmeira et al. 2009). There has not been a previous report of schistosome vaccine-mediated antigen-specific IgG transfer from mother to placenta. However, a 63 kDa S. mansoni protein and IgG-specific to this antigen have been detected in umbilical cord blood from schistosome-infected women and in their newborns (Attallah et al. 2003). Evaluation of cord blood mononuclear cells from schistosome-infected mothers have indicated sensitization of neonates that is thought to occur in utero, and which could be due either to circulating schistosomal antigens or to anti-idiotypic antibodies which cross the placenta during gestation (Novato-Silva et al. 1992). Similarly, circulating anodic antigens and associated Schistosoma mattheei-specific antibodies have been shown to transfer from the schistosome-infected mother cow to calves (Gabriel et al. 2002, 2005). However, what role and the extent to which these transplacental transferred antibodies play in conferring protection against schistosome infection needs to be elucidated.

Overall, the Sm-p80-based vaccines have shown distinct prophylactic, anti-fecundity, and therapeutic efficacy as well as is effective against both intestinal and urinary schistosomiasis (Ahmad et al. 2009b, 2011; Karmakar et al. 2014a, b; Zhang et al. 2010). These vaccine data are further enhanced by the detection of long-lasting, potent, and protective Sm-p80 vaccine-mediated humoral responses observed in the present study. Thus, another important milestone in the development pipeline of the vaccine has successfully been met. In addition, proof of concept studies in nonhuman primates and initial process development has been completed and the recombinant Sm-p80/GLA-SE vaccine, “SchistoShield®,” is now entering cGMP compliant manufacturing leading to an IND filing in the next 2–3 years with the final goal of Phase I/II human clinical trials as soon as 2017. We reiterate that a rational, judicious, and practical approach to the control of schistosomiasis should consist of Mass Drug and Vaccine Administration (MDVA), a dissemination approach that would involve treating infected individuals with praziquantel and then vaccinating them with a schistosome vaccine; especially one that is effective against the three major species of schistosomes that cause over 90 % of the disease, i.e., with a vaccine like SchistoShield®.

Acknowledgments

This work is supported by a grant from the NIAID/NIH (R01AI071223) to Afzal A. Siddiqui; NIH grants (P40RR012317, P40OD010431 and P40OD010988) to Gary L. White and Roman F. Wolf; SBIR/NIH grant (1R43AI103983) to Darrick Carter and Afzal A. Siddiqui; Bill and Melinda Gates Foundation grant (OPP1055855) to Steven G. Reed and Darrick Carter. Snails were provided by the Schistosome Research Reagent Resource Center for distribution by BEI Resources, NIAID, NIH: Schistosoma mansoni, strain NMRI exposed Biomphalaria glabrata, strain NMRI, NR-21962.

Contributor Information

Weidong Zhang, Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, 3601 4th Street, Mail Stop 6591, Lubbock, TX 79430, USA; Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Gul Ahmad, Department of Natural Sciences, School of Arts & Sciences, Peru State College, Peru, NE 68421, USA.

Workineh Torben, Tulane National Primate Research Center, Covington, LA 70433, USA.

Raymond T. Damian, Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA

Darrick Carter, Infectious Disease Research Institute, Seattle, WA 98102, USA; PAI Life Sciences, Seattle, WA 98102, USA.

Steven G. Reed, Infectious Disease Research Institute, Seattle, WA 98102, USA

Afzal A. Siddiqui, Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, 3601 4th Street, Mail Stop 6591, Lubbock, TX 79430, USA Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

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