Dataset Information

Induction of neutralizing antibodies by human papillomavirus vaccine generated in mammalian cells.

ABSTRACT:

Background

Cervical cancer caused by human papillomavirus (HPV) infections is one of the most common cancers affecting women worldwide. Current preventative HPV vaccines on the market are composed of HPV L1 protein produced either in the yeast such as Gardasil or in the insect cells such as Cervarix. The duration of efficacy and cross-protection remain highly desirable for the improvement of current prophylactic HPV vaccine. Given that HPV carries out infection and replicates in mammalian cells, L2 protein, which is not included in the current licensed vaccines, is included in the third generation of HPV vaccine in pursuing of providing broader prevention. We hypothesize that a virus-like particle (VLP) consisting of HPV L1 plus L2 proteins generated in mammalian cells will present conformations more closely to native HPV, thus it will provide more durable and broader efficacy of prevention.

Methods

We took advantage of 293TT cells to produce VLP containing L1 and L2 proteins of HPV16 and HPV18, respectively.

Results

VLP particles of uniformed size and morphology were observed, and potent and broadly neutralizing antibodies were induced in mice and rabbits. In addition, compared to bivalent HPV vaccine of Cervarix, our HPV L1-L2 VLPs elicited higher titer of anti-sera, and the anti-sera also presented comparable neutralization potency against HPV16 and HPV18 infections even a much less potent adjuvant was used in our case.

Conclusion

Our VLPs were capable of eliciting stronger and more broadly neutralizing activities against various HPV subtypes and were potential candidate HPV vaccines.

SUBMITTER: Wu X

PROVIDER: S-EPMC7990147 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The highly efficacious human papillomavirus (HPV) vaccines contain virus-like particles (VLP) representing genotypes HPV16 and HPV18, which together account for approximately 70% of cervical cancer cases. Vaccine-type protection is thought to be mediated by high titer, type-specific neutralizing antibodies. The vaccines also confer a degree of cross-protection against some genetically-related types from the Alpha-9 (HPV16-like: HPV31, HPV33, HPV35, HPV52, HPV58) and Alpha-7 (HPV18-like: HPV39, HPV45, HPV59, HPV68) species groups. Cross-protection is coincident with the detection of low titer serum responses against non-vaccine types by vaccinees. Such antibodies may be the effectors of cross-protection or their detection may be useful as a correlate or surrogate. This study evaluated whether cross-neutralization of HPV types from the Alpha-9 species group is mediated by antibodies with a predominantly type-restricted specificity for HPV16 that nevertheless exhibit low affinity interactions with non-vaccine types, or by antibody specificities that demonstrate similar recognition of vaccine and non-vaccine types but are present at very low levels. Antibodies generated following Cervarix® vaccination of 13-14 year old girls were evaluated by pseudovirus neutralization, VLP ELISA and by enrichment of target antigen specificity using VLP-immobilized beads. Two-dimensional hierarchical clustering of serology data demonstrated that the antibody specificity profile generated by VLP ELISA was both quantitatively and qualitatively different from the neutralizing antibody specificity profile. Target-specific antibody enrichment demonstrated that cross-neutralization of non-vaccine types was due to a minority of antibodies rather than by the weak interactions of a predominantly type-restricted HPV16 antibody specificity. Furthermore, cross-neutralization of non-vaccine types appeared to be mediated by multiple antibody specificities, recognizing single and multiple non-vaccine types, and whose specificities were not predictable from examination of the serum neutralizing antibody profile. These data contribute to our understanding of the antibody specificities elicited following HPV vaccination and have potential implications for vaccine-induced cross-protection.