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Hypertension is a serious worldwide public health problem. The aim of this study is to design anti-hypertension angiotensin II (Ang II) vaccine using molecular biology and immunological method. This novel anti-hypertension vaccine, which is a chimeric protein named pHAV-4Ang IIs, presents four successive repeated Ang IIs as the functional epitope on the surface of the hepatitis A virus-like particle(HAVLP). In this study, pHAV-4Ang IIs was expressed using Bac-to-Bac Baculovirus Expression System. With the RT-PCR analysis, SDS-PAGE, western blot, IFA, electron microscope methods for identification of expression products, these results confirmed that stable expression of pHAV-4Ang IIs can be effectively achieved in infected sf9 cells. Spontaneous hypertensive rats (SHRs) were immunized with pHAV-4Ang IIs to test immunogenicity and pharmacodynamic action. The results showed that this anti-hypertension vaccine can induce high titer Ang II -specific IgG antibody for almost 10 weeks. When antibody titer reached the peak at 8th week, the mean systolic blood pressure (SBP) degraded approximately 23 mmHg compared with the PBS control group, and the mean diastolic blood pressure (DBP) degraded approximately 12 mmHg compared with the PBS control group. These results suggest that this anti-hypertension vaccine has good immunogenicity and good effect on reduction of blood pressure in SHRs, which provide reliable base for large-scale preparation of this hypertension vaccine in the future, and a new direction of exploration for the development of anti-hypertension therapeutic vaccine.

The immune response to hepatitis B surface antigen (HBsAg) is mostly genetically determined. Interleukin 10 (IL-10) is a central immunoregulatory cytokine with important effects on B-cells. We have studied the influence of IL-10 promoter polymorphisms on the immune response to HBsAg and hepatitis A vaccination. We vaccinated 202 twin pairs in an open prospective study with a combined recombinant HBsAg/inactivated hepatitis A vaccine. IL-10 promoter polymorphisms were investigated in all individuals and their influence on anti-HBs, and anti-HAV responsiveness was studied. In the multiple regression analysis accounting for smoking, gender, body mass index and age, the ACC haplotype (-1082, -819 and -592) had a strong influence on anti-HBs production. Individuals carrying the ACC haplotype had anti-HBs titres almost twice as high as individuals without this haplotype. In contrast, anti-HAV production was suppressed by the presence of the -1082A allele in comparison with individuals homozygous for the -1082G allele. The contribution of the shared IL-10 promoter haplotype accounted for 27% of the genetic influence on anti-HBs antibody response. In conclusion, genetic variability in the IL-10 promoter is an important modulator of the immune response against hepatitis viral antigens.

Objective: To study the genome sequence of hepatitis A virus L-A-1 strain which has been applied for live attenuated vaccine production in China, to compare with other HAV strains, to understand some characteristics of L-A-1 strain, and to find the mechanism of attenuation and cell adaptation., Methods: Genome fragments were prepared by antigen-capture PCR from infected cell (2BS), PCR products were cloned into T vector, sequenced and analyzed by using bioinformatics program., Results: Analysis of the genomic sequences(nt 25-7,418) showed that the open reading frame contains 6,675 nucleotides in length encoding 2,225 amino acids. Sequence homology comparison showed 98.00% and 94.00% homology at nucleotide level, and 98.51% and 98.65% homology at amino acid level with international strains MBB and HM 175, respectively. Through comparison with other attenuated, cell adapted and cytopathic effect (CPE) strains, L-A-1 strain had mutation at nt 152, 591, 646, 687 and insertion at nt 180-181 in 5?NTR and had mutation at nt 3,889 (aa 1 052-Val) in 2B region, these mutations and insertion are molecular basis for cell adaptation; mutation at nt 4,185 (aa 1 152-Lys) in 2C region should be attenuated marker; deletion in 3A region (nt 5,020-5,025) that caused two amino acids deletion is virus fast growth basis., Conclusion: Through analyzing L-A-1 strain genomic sequence, certain sites related to cell adaptation and attenuation were found.