Challenge studies in Rhesus monkeys immunized with candidate hepatitis E vaccines: DNA, DNA-prime-protein-boost and DNA-protein encapsulated in liposomes.
Complete ORF2 gene (1983bp) of hepatitis E virus (HEV) and the 450bp region within ORF2 containing neutralizing epitope (NE) cloned in pVAX1 and corresponding proteins expressed in baculovirus and prokaryotic systems respectively were evaluated as vaccine candidates. Two doses of liposome encapsulated DNA plus corresponding protein with both ORF2 and NE regions (Lipo-ORF2-DP and Lipo-NE-DP) showed 100% seroconversion and comparable anti-HEV titres in Swiss albino mice. These vaccine candidates were further evaluated as DNA, DNA-prime-protein-boost (DPPB) and liposome formulations in Rhesus monkeys. Monkeys receiving ORF2/NE DNA seroconverted after fourth dose while those immunized employing ORF2-DPPB format seroconverted at 7 weeks post third dose. In view of the delayed weak antibody response, these monkeys were not challenged. Though Lipo-ORF2-DP was immunogenic, 2 of the 4 monkeys developed HEV infection following homologous virus challenge of 100 Monkey Infectious Dose(50). Both monkeys immunized with Lipo-NE-DP and 1 of the 2 monkeys immunized with NE-DPPB showed complete protection, the second monkey being protected from hepatitis with limited viral replication. Irrespective of the type of immunogen, all challenged monkeys were protected from hepatitis. The results document Lipo-NE-DP to be a promising vaccine candidate needing further evaluation.
Arankalle
Vidya A
VA
Hepatitis Division, National Institute of Virology, Microbial Containment Complex, Sus Road, Pashan, India. varankalle@yahoo.com
Lole
Kavita S
KS
Deshmukh
Tejaswini M
TM
Srivastava
Shubham
S
Shaligram
Umesh S
US
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000276:immunology / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D008081:Liposomes / Q000494:pharmacology*; D008253:Macaca mulatta; D051379:Mice; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006508:Hepatitis Antibodies; D008081:Liposomes; C400971:ORF2 protein, Hepatitis E virus; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins