Progress in L2-Based Prophylactic Vaccine Development for Protection against Diverse Human Papillomavirus Genotypes and Associated Diseases

Abstract

The human papillomaviruses (HPVs) are a family of small DNA tumor viruses including over 200 genotypes classified by phylogeny into several genera. Different genera of HPVs cause ano-genital and oropharyngeal cancers, skin cancers, as well as benign diseases including skin and genital warts. Licensed vaccines composed of L1 virus-like particles (VLPs) confer protection generally restricted to the ≤9 HPV types targeted. Here, we examine approaches aimed at broadening the protection against diverse HPV types by targeting conserved epitopes of the minor capsid protein, L2. Compared to L1 VLP, L2 is less immunogenic. However, with appropriate presentation to the immune system, L2 can elicit durable, broadly cross-neutralizing antibody responses and protection against skin and genital challenge with diverse HPV types. Such approaches to enhance the strength and breadth of the humoral response include the display of L2 peptides on VLPs or viral capsids, bacteria, thioredoxin and other platforms for multimerization. Neither L2 nor L1 vaccinations elicit a therapeutic response. However, fusion of L2 with early viral antigens has the potential to elicit both prophylactic and therapeutic immunity. This review of cross-protective HPV vaccines based on L2 is timely as several candidates have recently entered early-phase clinical trials.

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

“…Nevertheless, some studies have shown that the conserved region near the N-terminus of L2 protein may induce cross-neutralizing antibodies against highly divergent HPV types and can be single-expressed in bacteria. (Karanam et al, 2009;Schellenbacher et al, 2017;Olczak and Roden, 2020). Thus, this finding proposed the HPV L2 become a potential antigen candidate for the broad Medicine,Public Health,and Nursing,Universitas Gadjah Mada,Yogyakarta,Indonesia.…”

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

“…This region is known as essential for L2 infection mechanisms as cell surface exposure site, furin cleavage sites right before entering the host's cell, DNA binding domains, and localization of cell nucleus signals (11). Several studies have also shown that the L2 N-terminus region potentially induces cross-neutralizing antibodies and promises to be a broad HPV vaccine epitope candidate (14,22,(37)(38)(39). The low-cost L2-based vaccine strategy may become a possible alternative compared to the high cost of the L1-based vaccine available (40).…”

“…Nevertheless, some studies have shown that the conserved region near the N-terminus of L2 protein may induce cross-neutralizing antibodies against highly divergent HPV types and can be single-expressed in bacteria. This nding proposed the HPV L2 to become a potential antigen candidate for the broad HPV vaccine (12)(13)(14).…”

An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy

“…A display of L2 peptides on bacteria, viral capsids, or VLPs and other platforms are examples of techniques to improve the strength of the humoral response. L2-based vaccines have no therapeutic potential on their own, but when combined with viral oncoproteins, E6 and E7, they may generate both preventive immunity and therapeutic immunity ( 80 ). Even without adjuvant, mice inoculated with a single dose of MS2–16L2 VLPs were partially protected against challenge with a high dose of HPV16 1 year later ( 81 ).…”