Immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent E7E6 fusion proteins from human papillomavirus types 16 and 18.

BACKGROUND

Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer, HPV16 and HPV18 and occurs in 50% and 20% of cases of cervical cancer, respectively. The viral oncogenes E6 and E7 which is Rabbit Recombiant Proteins constitutively expressed by tumor cells related to HPV and can therefore be used as a target antigen for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing HPV16 / 18 E7E6 fusion proteins (rVVJ16 / 18E7E6) to be used as a therapeutic vaccine for the treatment of cancer HPV16⁺ and HPV18⁺.

METHOD

We construct a recombinant vaccinia virus expressing bivalent modified E7E6 fusion proteins of HPV types 16 and 18 (rVVJ16 / 18E7E6) based on vaccinia virus Tiantan strain. We then define the cellular immune response against the virus in mice and rhesus monkeys and assessed the antitumor efficacy of this response in mice using TC-1 tumor challenge models.

RESULTS

Our data show that rVVJ16 / 18E7E6 able to obtain various levels CD8⁺ T cell immune response and lysis of target cells in mice in response to the peptide HPV16E7₄₉₋₅₇ and HPV18E6₆₇₋₇₅. In addition, the virus is also capable of inducing an anti-tumor response in HPV16⁺ TC-1 tumor challenge models, including the partial protection (30-40%) and delayed tumor appearance. In addition, this virus is able to induce immune responses in rhesus monkeys.

CONCLUSION

Recombinant vaccinia virus rVVJ16 / 18E7E6 can produce a clear cellular immunity and significant in both mice and rhesus monkeys. These data provide the basis for the use of recombinant viruses as potential vaccine candidates for further study.

[Induction of protective immunity in rhesus monkeys by inoculation with a recombinant fusion protein of the cholera toxin B-subunit of multivalent epitopes from Plasmodium falciparum].

Rhesus monkeys (5 in each group) were inoculated with the recombinant fusion protein of the cholera toxin B subunit and multi-valent epitope of Plasmodium falciparum intranasal or intramuscular (i.m.). Immune responses and protective effects were evaluated. The antibody titer (Geometric mean) against CTB reached 1: 512 (intranasal) and 1: 10,000 (i.m.) 14 days after the 3rd immunization, and antibodies against P. falciparum is also described, titer in i.m. The group was also significantly higher than the intranasal group.

 Monkeys were challenged with 1.25 x 10 (8) sporozoites P. cynomolgi, Patent infections observed in all 5 monkeys in the control group inoculated with PBS in 10-14 days after challenge. Patent infection was also observed in 5 animals were inoculated via the intranasal and 2 animals on the 19th day after the intramuscular group challenge, but Sheep Recombinant Proteins infections that last only 4 days in 3 animals in intranasal group and 2 animals in the group of muscles. 

The results demonstrated that the candidate vaccine could induce protective immune responses in rhesus monkeys against challenge P. cynomolgi.