RG1-VLP and Other L2-Based, Broad-Spectrum HPV Vaccine Candidates

Abstract

Licensed human papillomavirus (HPV) vaccines contain virus-like particles (VLPs) self-assembled from L1 major-capsid proteins that are remarkably effective prophylactic immunogens. However, the induced type-restricted immune response limits coverage to the included vaccine types, and costly multiplex formulations, restrictive storage and distribution conditions drive the need for next generation HPV vaccines. Vaccine candidates based upon the minor structural protein L2 are particularly promising because conserved N-terminal epitopes induce broadly cross-type neutralizing and protective antibodies. Several strategies to increase the immunological potency of such epitopes are being investigated, including concatemeric multimers, fusion to toll-like receptors ligands or T cell epitopes, as well as immunodominant presentation by different nanoparticle or VLP structures. Several promising L2-based vaccine candidates have reached or will soon enter first-in-man clinical studies. RG1-VLP present the HPV16L2 amino-acid 17–36 conserved neutralization epitope “RG1” repetitively and closely spaced on an immunodominant surface loop of HPV16 L1-VLP and small animal immunizations provide cross-protection against challenge with all medically-significant high-risk and several low-risk HPV types. With a successful current good manufacturing practice (cGMP) campaign and this promising breadth of activity, even encompassing cross-neutralization of several cutaneous HPV types, RG1-VLP are ready for a first-in-human clinical study. This review aims to provide a general overview of these candidates with a special focus on the RG1-VLP vaccine and its road to the clinic.

Cervical Human Papillomavirus Infection (HPV) and High Oncogenic Risk Genotypes among Women Living with HIV in Asia: A Meta-Analysis

“…In Asia, the scaling-up of antiretroviral therapy programs seems to be effective for protecting WLHIV from oncogenic HPV infection. HPV-16 was the most frequent genotype, but closely followed by HPV-52, -58, -18, and -33, which underlines the need for immunization programs based on nonavalent or new generation vaccines to fight cervical cancer in these women [ 39 ].…”

“…The prevalence of HR-HPV infection overall and by oncogenic genotype was calculated as the number of WLHIV harboring any of the 13 oncogenic genotypes, divided by the total number of women who underwent HPV testing. The 13 oncogenic genotypes (16,18,31,33,35,39,45,51,52,56,58,59,68) were considered based on the WHO classification [3].…”

Human Papillomavirus Type 16 L2 Gene Sequence Variation Analysis in Indonesian Cervical Cancer Specimens

“…L2 also proposes as a broadly neutralizing epitope, especially in the region near the N-terminus at amino acid residue 17-36, 58-64, 64-73, and some other segments beyond the rst 120 residues (21)(22)(23). A study on HPV16 L2 gene variation should be essential for future research about their differences in pathogenicity in cervical cancer, as well as recognizing their phylogenetic sub-linages.…”

Prevalence of High-Risk Human Papillomavirus Infections before and after Cervical Lesion Treatment, among Women Living with HIV

“…This high frequency was also evidenced among perinatally infected women in Thailand and Vietnam [ 7 ], emphasizing the need to scale-up nonavalent HPV vaccination programs in South-East Asia, at least among women living with HIV. The ongoing development of new L2-based vaccines may be promising for overcoming the diversity of oncogenic and potentially oncogenic HPV genotypes [ 17 ].…”