title: A DNA-prime/protein-boost vaccination regimen enhances Th2 immune responses but not protection following Schistosoma mansoni infection.
abstract: 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. adadara@hsph.harvard.edu
authors.forename: Akram A
authors.initials: AA
authors.lastname: Da'Dara
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Skelly
authors.forename: Christine M
authors.initials: CM
authors.lastname: Walker
authors.forename: Donald A
authors.initials: DA
authors.lastname: Harn
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D051379:Mice; D008810:Mice, Inbred C57BL; D010270:Parasite Egg Count; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C067614:antigen Sm23, Schistosoma