Human Papillomavirus L1 Virus-like Particle Vaccine Research Articles

Enhancement of humoral and cell mediated immune response to HPV16 L1-derived peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like particle vaccine in healthy females

Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are employed with great success for the prevention of HPV infection. However, limited information is available regarding the immune responses against human papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination, primarily due to the lack of widely used assays for immune monitoring. The aim of the present study was to identify HPV16 L1-derived B and T cell epitopes for monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy females. The levels of immunoglobulin G (IgG), IgE, IgA and IgM reactive to HPV16 L1-derived peptides were measured by multiplex bead suspension assay. Following detailed B cell epitope mapping, T cell responses specific to HPV16 L1-derived peptides were evaluated by an IFN-γ ELISPOT assay. The levels of IgG, IgM and IgA reactive to 20-mer peptides (PTPSGSMVTSDAQIFNKPYW) at positions 293-312 and 300-319 of HPV16 L1 were significantly increased in the plasma after 2, 7, and 12 months after first vaccination. Detailed epitope mapping identified the amino acid sequence (TSDAQIFNKP) at position 301-310 of HPV16 L1 as an immunogenic B cell epitope. In addition, T cell responses to an HLA-A2- and HLA-A24-restricted epitope (QIFNKPYWL) at position 305-313 of HPV16 L1 were increased following immunization, suggesting that the HPV16/18 L1-VLP vaccination as able to induce specific immune responses in T and B cells simultaneously. The identified B and T cell epitopes may be useful as a biomarker for monitoring the immune responses subsequent to HPV16/18 L1 VLP vaccination. Thus, the present study may provide novel information to improve the understanding of the immune responses to HPV16 L1.

Development of Human Papillomavirus (HPV) Vaccines: A Review of Literature and Clinical Update

The casual relationship concerning Human papillomaviruses (HPV) and cervical cancer is already established. Therefore, such HPV-associated malignancies might be prevented by prophylactic HPV vaccines. From 2009, two prophylactic HPV L1 Virus-Like Particle vaccines namely, Gardasil®; - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline) are widely commercially available. By Aug 2014, 58 countries had introduced HPV vaccination in their national immunization program; this has led to numerous publications on safety and real world effectiveness. We have also seen long-term immunogenicity and efficacy data emerging. Data on cross-protection has also evolved. In clinical trials, it is observed that vaccinating adolescents results in higher immunological response than young adults hence to achieve best HPV vaccine efficacy it is advisable to immunize before the onset of sexual activity. Recently we have seen development of 2 dose vaccine schedule for adolescent, and emerging evidences even point that single dose of HPV vaccines can result in high efficacy, this observation is currently under consideration but if accepted will greatly impact vaccination coverage. In terms of safety, pregnancy registry did not find any unexpected patterns in fetal or maternal outcomes. This review only focuses on the efficacy and safety data of both Food and Drug Administration approved vaccines from clinical phase I to phase IV.

HPV vaccination with Gardasil®: a breakthrough in women’s health

Human papillomavirus (HPV) represents one of the most common sexually transmitted infections. Although infection is often self-limited, a percentage of women with HPV infection will go on to develop cervical precancerous or cancerous lesions. It is estimated that HPV16 is responsible for approximately half of all cervical cancers worldwide. Several studies have tested vaccines directed against specific HPV types, namely types 6, 11, 16 and 18. This paper reviews these studies, particularly focusing on a quadrivalent (type 6, 11, 16 and 18) HPV L1 virus-like particle vaccine under investigation in Phase III trials at present. Data indicate that this vaccine, referred to as Gardasil®, can prevent precancerous cervical lesions and early in situ cervical cancers with few adverse effects, and the vaccine has been approved by the FDA for this indication. Another vaccine, HPV16 L1, directed solely against HPV16, has also been demonstrated to be effective (at present, follow-up has been for up to 48 months) in providing protection against persistent infection with this viral strain and preventing HPV16-related cervical intraepithelial neoplasia 2/3, while producing minimal adverse effects in recipients. Given the lack of a pharmacological intervention that can eradicate HPV in infected individuals and the prevalence of cervical cancer secondary to HPV infection across the world, the HPV vaccine represents a significant breakthrough in women’s health.

A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine

Human papillomavirus (HPV) infection can cause genital warts and cervical cancer. HPV types 6 and 11 cause >90% of genital wart cases; HPV16 and 18 cause 70% of cervical cancers. A prophylactic HPV (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine may substantially reduce the incidence of these lesions. This report describes the results of a phase I study of the HPV18 component of such a vaccine. Forty women were randomized to receive either HPV18 L1 VLP vaccine or placebo. Anti-HPV18 responses were measured using a competitive radioimmunoassay (cRIA). Tolerability was evaluated using vaccination report cards (VRC). The study showed that the HPV18 L1 VLP vaccine was generally well-tolerated and highly immunogenic. Peak anti-HPV18 geometric mean titers (GMT) in vaccines were 60-fold greater than those observed in women following natural HPV18 infection. Further studies of a multivalent HPV L1 VLP vaccines are warranted.