DNA immunization represents a promising
vaccine strategy that has been reasonably successful, and will likely play an even greater role in
vaccine development as these
vaccines continue to be improved. We have developed a partially protective
DNA vaccine against schistosome
infection based on a 23-kDa
integral membrane protein, Sm23. The focus of this study was to compare immunogenicity and efficacy of vaccination regimens utilizing Sm23
DNA vaccine alone vs. regimens that utilized both Sm23
DNA and Sm23 in
recombinant protein form. We found that priming and boosting with the Sm23
DNA construct (Sm23-pcDNA) resulted in a significant level of protection against challenge
infection (36-44%). In contrast, altering this protocol by changing the boost from Sm23
DNA to boosting with recombinant Sm23
protein (rSm23) formulated in
aluminium hydroxide (
alum) failed to induce a significant reduction in worm burdens. Similarly, mice primed and boosted with the rSm23 in
alum also did not develop significant levels of protection against challenge
infection. We hypothesize that the differences in the ability to drive protective immunity using the
DNA prime-
DNA boost strategy and the inability to do so when recombinant Sm23 in
alum was substituted for Sm23
DNA is due to driving of different immune responses. In support of this, we found that mice primed and boosted with Sm23-pcDNA had Th1-type immune responses characterized by low anti-Sm23
IgG1 :
IgG2a antibody isotype ratios, whereas mice boosted with rSm23 had higher
IgG1 :
IgG2a ratios. In addition, priming and boosting with rSm23 elicited mainly
IgG1 antibodies with no detectable
IgG2a, indicative of a polarized Th2-type immune response. Thus, similar to our earlier work, the results of this study show that protective vaccination using Sm23 is associated with a Th1 immune response, and efficacy is diminished using protocols that diminish this Th1 bias. In our study, this was likely due to the use of the Th2-driving adjuvant
alum, and future studies are planned where we will compare the protective efficacy of rSm23 administered with Th1-type adjuvants.