Immunogenicity of a trivalent human papillomavirus L1 DNA-encapsidated, non-replicable baculovirus nanovaccine.
Previously, we developed a non-replicating recombinant baculovirus coated with human endogenous retrovirus envelope protein (AcHERV) for enhanced cellular delivery of human papillomavirus (HPV) 16L1 DNA. Here, we report the immunogenicity of an AcHERV-based multivalent HPV nanovaccine in which the L1 segments of HPV 16, 18, and 58 genes were inserted into a single baculovirus genome of AcHERV. To test whether gene expression levels were affected by the order of HPV L1 gene insertion, we compared the efficacy of bivalent AcHERV vaccines with the HPV 16L1 gene inserted ahead of the 18L1 gene (AcHERV-HP16/18L1) with that of AcHERV with the HPV 18L1 gene inserted ahead of the 16L1 gene (AcHERV-HP18/16L1). Regardless of the order, the bivalent AcHERV DNA vaccines retained the immunogenicity of monovalent AcHERV-HP16L1 and AcHERV-HP18L1 DNA vaccines. Moreover, the immunogenicity of bivalent AcHERV-HP16/18L1 was not significantly different from that of AcHERV-HP18/16L1. In challenge tests, both bivalent vaccines provided complete protection against HPV 16 and 18 pseudotype viruses. Extending these results, we found that a trivalent AcHERV nanovaccine encoding HPV 16L1, 18L1, and 58L1 genes (AcHERV-HP16/18/58L1) provided high levels of humoral and cellular immunogenicity against all three subtypes. Moreover, mice immunized with the trivalent AcHERV-based nanovaccine were protected from challenge with HPV 16, 18, and 58 pseudotype viruses. These results suggest that trivalent AcHERV-HPV16/18/58L1 could serve as a potential prophylactic baculoviral nanovaccine against concurrent infection with HPV 16, 18, and 58.
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Hansam
H
Cho
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Hee-Jung
HJ
Lee
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Yoon-Ki
YK
Heo
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Yeondong
Y
Cho
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Yong-Dae
YD
Gwon
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Mi-Gyeong
MG
Kim
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Ki Hoon
KH
Park
College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Yu-Kyoung
YK
Oh
Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
Young Bong
YB
Kim
D000818:Animals; D016367:Baculoviridae / Q000235:genetics* / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics*; D020077:Endogenous Retroviruses / Q000235:genetics; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D061987:Sf9 Cells; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; C063317:L1 protein, Human papillomavirus type 16; C480565:L1 protein, Human papillomavirus type 18