Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4.
Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 microg) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1-2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2-3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 x 10(4) genome equivalents of HEV, regardless of the genotype. After challenge with 5 x 10(5) genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.
Huang
W J
WJ
Department of Cell Biology, National Institute for the Control of Pharmaceutical and Biological Products, No. 2 Tiantanxili, Chongwen District, 100050, Beijing, China.
Zhang
H Y
HY
Harrison
T J
TJ
Lan
H Y
HY
Huang
G Y
GY
Wang
Y C
YC
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005243:Feces / Q000821:virology; D016751:Hepatitis E / Q000517:prevention & control*; D016752:Hepatitis E virus / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D017201:Virus Shedding
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D007074:Immunoglobulin G; C400971:ORF2 protein, Hepatitis E virus; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D014764:Viral Proteins; C041524:aluminum sulfate; D000410:Alanine Transaminase