Abstract
Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.
Highlights
Virus-like particles (VLPs) are empty viral shells derived from the expression, in a suitable host cell, of viral structural proteins such as capsid or coat proteins
Recent studies show that a single based on virus-like particles (VLPs) derived from over-expression of the capsid proteins in yeast (Gardasil vaccines) or dose of the Human papillomaviruses (HPVs) VLP‐based vaccine can lead to long‐lasting protection from HPV infection [21]
Unlike antibodies elicited against L1 VLPs, antibodies elicited against an L2 peptide representing amino acids 1–88 from HPV type 18 or even from L2 of bovine papillomavirus (BPV) cross-protect, albeit at low titers, against diverse mucosal (HPV6, 11, 16, 18, 31) and cutaneous HPV types (HPV5) [37,38,39,40,41]
Summary
Virus-like particles (VLPs) are empty viral shells derived from the expression, in a suitable host cell, of viral structural proteins such as capsid or coat proteins. The small size of VLPs enables them to be transported to the lymphoid organs within a short period of time and to be efficiently taken up by APCs for presentation to T-helper cells [9]. VLP-based prophylactic vaccines have been approved by the Food and Drug Administration to protect (ii) VLPs have virally encoded T‐helper cell and epitopes, which enhance activation. T‐helper cells secret cytokines, leading to the activation three VLP-based HPV vaccines (Gadarsil-9, Cervarix, and Gardasil-4 (discontinued in the US)) have of B‐. Bacteriophage coat proteins (from MS2, PP7, etc.) have the potential to encapsudate ssRNA that
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