Sm29, but Not Sm22.6 Retains its Ability to Induce a Protective Immune Response in Mice Previously Exposed to a Schistosoma mansoni Infection

Abstract

BackgroundA vaccine against schistosomiasis would have a great impact in disease elimination. Sm29 and Sm22.6 are two parasite tegument proteins which represent promising antigens to compose a vaccine. These antigens have been associated with resistance to infection and reinfection in individuals living in endemic area for the disease and induced partial protection when evaluated in immunization trials using naïve mice.Methodology/principals findingsIn this study we evaluated rSm29 and rSm22.6 ability to induce protection in Balb/c mice that had been previously infected with S. mansoni and further treated with Praziquantel. Our results demonstrate that three doses of the vaccine containing rSm29 were necessary to elicit significant protection (26%–48%). Immunization of mice with rSm29 induced a significant production of IL-2, IFN-γ, IL-17, IL-4; significant production of specific antibodies; increased percentage of CD4+ central memory cells in comparison with infected and treated saline group and increased percentage of CD4+ effector memory cells in comparison with naïve Balb/c mice immunized with rSm29. On the other hand, although immunization with Sm22.6 induced a robust immune response, it failed to induce protection.Conclusion/significanceOur results demonstrate that rSm29 retains its ability to induce protection in previously infected animals, reinforcing its potential as a vaccine candidate.

Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

“…When C57Bl/6 mice were vaccinated with Sm22.6 and challenged 15 days after the last boost, they showed a mean 34.5 % protection [ 59 ]. In contrast, when the antigen was administered to Balb/c mice that were challenged 30 days after the last boost, the protection elicited was 0 and 18 % [ 60 ]. A similar pattern was observed with Sm29 where 51 % protection was observed after a challenge of C57Bl/6 mice at 15 days after the last boost [ 61 ] and 0 % protection after a challenge of Balb/c mice at 30 days [ 60 ].…”

Characterization of memory T cells in individuals resistant to Schistosoma mansoni infection

“…In schistosomiasis, several immunization strategies with different parasite antigens have been developed and the most promising results have demonstrated the participation of memory cells in the context of protection or reduction of tissue damage caused by the presence of the parasite …”

T cell mediated immunity to Schistosoma japonicum infection and vaccination

“…Vaccination with rSjTPI-LD1 induced a significantly high level of both anti-rSjTPI and anti-rSjLD1-specific IgG antibodies at all time points post-vaccination compared with controls ( Figure 4.1). This is a feature common to other schistosome vaccine candidates tested in mice [280,281]; moreover, another study showed that IgG antibodies are important for the protection against schistosomes [282]. Here, the anti-rSjTPI and anti-rSjLD1 IgG antibody response peaked at week 6 after the last booster vaccination with the highest titers of 1:102,400 and1: 204,800 obtained, respectively (Figure 4.2).…”

“…A recent report [280] has suggested that undertaking anti-schistosome vaccine trials in mice may be problematic and may generate spurious protective data. The report questioned whether such trials in mice are able to effectively determine whether any significant worm reduction data obtained are due to acquired immunity induced by a candidate vaccine or are rather due to mouse vasculature physiology that impacts on schistosome worm survival [279].…”

“…There are reports that Sm29 in recombinant form can prevent infection in animals previously exposed to S. mansoni. For example, 26-48% protection was observed in BALB/c mice that were previously infected with the LE strain of S. mansoni and treated with PZQ [137].…”