The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.
Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.
Ramachandran
Sabarinathan
S
Centre for Biotechnology, Anna University, Chennai, India.
Kumar
Mishra Pankaj
MP
Rami
Reddy Maryada Venkata
RM
Chinnaiah
Harinath Basker
HB
Nutman
Thomas
T
Kaliraj
Perumal
P
McCarthy
James
J
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017178:Brugia malayi / Q000235:genetics / Q000276:immunology*; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004605:Elephantiasis, Filarial / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D018509:DNA, Helminth; D015801:Helminth Proteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA