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The Combination of Aluminum Adjuvant and CpG Adjuvant can Enhance the Immunogenicity of Recombinant HPV Vaccines

Juyin Li, Xiaoyu Xia, Xiao Dong Wang, Jiaojiao Sun, Changyao Tan, Tong Zhou, Jianhui Zhang, Srikanth Babu BMV, Bao Mengru, Xuan Liang, Jianqiang Li, Jun Ge, Xiuying Pu

Prophylactic vaccination and early detection of cervical cancers can effectively prevent Human Papilloma Virus (HPV) infection. HPV major capsid protein (HPV L1), a coat protein assembles into Virus-Like Particles (VLPs), acts as a potent immunogen. In the present investigational study, we evaluated the role of the combination effect of the aluminum adjuvant and TLR-9 agonist Cytosine phosphoguanine (CpG) on the immune response and the antigen dose-sparing effect.

HPV L1 VLPs for types 16/18/52 and 58 have been produced by a gene expressed in Hansenula polymorpha. Bivalent (16,18) and tetravalent (16,18,52,58) vaccines with mono (Al+) and biadjuvanted (Al+CpG) were formulated by adsorbing purified VLPs onto aluminum hydroxide and CpG. Sera collected from immunized BALB/c mice showed that biadjuvanted vaccines elicits significantly higher anti-HPV neutralizing antibodies than monoadjuvanted vaccines. Full-dose biadjuvant vaccines (4 μg) elicits 2.5 times higher neutralizing antibodies than half-dose vaccine and no significant differences were observed between the full-dose monoadjuvant vaccine (Al+) and the half-dose biadjuvant vaccine (Al+CpG). Immunised mice have distinct levels of secreted IgG antibodies and the vaccines formulated with a aluminium and CpG, a TLR-9 agonist had skewed towards high Th1 biased immune response with an elevated IgG2a/IgG1 ratio.

In conclusion, recombinant HPV vaccines formulated with an immune modulating CpG agonist and an adjuvant can induce a greater immune response. This combination of CpG and alum effectively reduces the dose of the HPV L1 vaccine by 2.5 times and makes the availability of vaccines at an affordable price.