[Immune response for phase I clinical trial of a hepatitis B immunogenic complex therapeutic vaccine, YIC].
OBJECTIVE
A hepatitis B immunogenic complex therapeutic vaccine, yeast-derived recombinant HBsAg combined with human anti-HBs immunoglobulin (YIC), was evaluated for safety and immune response in phase I clinical trial.


METHODS
The subtypes IgG1, IgG2, IgG3 and IgG4 of serum anti-HBs collected from 20 immunized subjects were analyzed by ELISA. The lymphocyte proliferation assay was carried out in five subjects and was analyzed by 3H-thymidine incorporation. The assays for IFNgamma, IL-2, IL-4, IL-6, IL-10 and TNFalpha were measured using Human Cytometric Bead Array Kit with FACSCalibur.


RESULTS
The results showed that the subtypes of anti-HBs antibodies induced by 30, 60 and 90 microg YIC-immunized groups among all of the adult volunteers (20/20) were IgG1 and IgG3. The level of IgG1 was higher than that of IgG3 in each volunteer but the strength was different from each other. The rHBsAg-stimulated lymphocyte proliferation induced by three injections of 90 microg of YIC showed that the stimulation index was more than 2.0 in four out of the five individuals (4/5), ranging from 2.70 to 4.75. PHA-stimulated lymphocyte proliferation was not related to rHBsAg-stimulated lymphocyte proliferation. In the 60 microg YIC-immunized group there was no significant difference between the levels of IFNgamma, IL-2, IL-4, IL-6 and IL-10 at day 0 and day 42. At day 71, in comparison to day 0, the level of IFNgamma was higher in all eight subjects studied (P = 0.015) and the level of IL-2 was also increased in seven out of eight subjects (P = 0.002). In contrast, the levels of IL-4, IL-6, IL-10 and TNFalpha showed no significant difference in all the subjects (P-values: 0.298, 0.976, 0.202 and 0.996).


CONCLUSIONS
Our results indicate that this hepatitis B immunogenic complex therapeutic vaccine (YIC) can induce a potent anti-HBs response.
Liu
Shun-ai
SA
Beijing Ditan Hospital, Beijing 100011, China.
Xu
Dao-zhen
DZ
Zhang
Jian-ping
JP
Huang
Ke-lin
KL
Yao
Jun
J
Xu
Li-feng
LF
Yuan
Zheng-hong
ZH
Wen
Yu-mei
YM
D000293:Adolescent; D000328:Adult; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000628:therapy*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic