Virus-like Particle-Based L2 Vaccines against HPVs: Where Are We Today?

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.

Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers

“…But because the L1 is not conserved between different types of HPV, the researchers have also focused on L2 based vaccine development [189,190]. However, the L2 challenge is its inability to form VLP [189,191]. The concatemers consists of tandem or conserves sequences of several HPV types were designed on the MS2 bacteriophage-based VLP vaccine and the mice immunized with the construct produced high antibody titers.…”

Systematic Review and Meta-Analysis of the Efficacy of Nanoscale Materials Against Coronaviruses—Possible Potential Antiviral Agents for SARS-CoV-2

“…The coat proteins that form the capsid, enhance T-cell activation, the nanoscale size and endogenous adjuvant features of virus-like particles have been credited for making them more immunogenic. A number of nano-virus-like particle-based vaccines have been successfully tested against human papillomaviruses and H1N1 influenza virus [68], [69]. The other virus-like particles included studies in the present paper demonstrate that the chimeric virus-like particles are suitable candidates for vaccine development, especially those against MERS-CoV and SARS-CoV [29], [32], [38].…”

Bacterial-Derived Outer Membrane Vesicles are Potent Adjuvants that Drive Humoral and Cellular Immune Responses

“…Vaccines using inactivated virus or live-attenuated viral strains have been tremendously successful in preventing diseases like polio, measles, and smallpox, whereas toxoid and subunit-based vaccines have been highly effective in preventing bacterial diseases like tetanus and bacterial meningitis, respectively [1]. Over the past decade, advances in nanotechnology have facilitated the development of nanoparticle-based vaccines that are approved for use in the United States and elsewhere [2,3]. For example, viral-like particles (VLP) and outer-membrane vesicles (OMV) form the basis of the FDA-licensed vaccines, Gardasil and Bexsero, for the prevention of human papilloma virus and Neisseria meningitidis serogroup B, respectively [4,5].…”