HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection

Abstract

Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix™ induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p<0.001; HPV45, p<0.001) and correlated with HPV16/18 neutralizing titers, respectively. These findings raise the possibility that cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine.

Burden of Cervical, Anal, and Oral HPV in an Inner-City Pre-vaccine Adolescent Population

“…This highlights the importance of early vaccination, although vaccinating sexually active adolescents may still provide a benefit, either against other HPV types targeted by the vaccine (e.g., for HPV16 among those HPV-DNA positive for HPV18 only and vice versa, which still include the majority of adolescents tested), or for phylogenetically related alpha-9 and -7 HPV types (e.g., HPV31 and 45) that may benefit from cross-protection. 12,13 This study shows only moderate concordance in detection of HPV vaccine high-risk (HPV16 and 18) and related types (HPV31 and 45) between cervical and extra-cervical sites. Although the implications of prevalent anal or oral HPV infections on vaccine efficacy are unknown, this suggests post-vaccine surveillance studies of cervical, anal, and oral HPV in real-world settings and high-risk populations are warranted.…”

“…The majority of subjects (82 %) had had at least three sexual partners at the time of enrollment, and 53 % had four or more partners. The overall median age at first vaginal intercourse was 14 years (range [12][13][14][15][16][17][18][19], and history of sexually transmitted infections (STIs; 47 %) was high, including for Chlamydia (33 %). Over a third of cervical Paps collected at enrollment showed atypical cells of undetermined significance (ASCUS; 23 %) or presence of squamous intraepithelial lesions (LSIL 15 %/HSIL 1 %).…”

Virus Like Nanoparticles: Display Matters

“…Many viral surface antigens have the ability to selfassemble into VLPs that resemble the native viral particles in appearance, for example, in case of Human Papillomavirus (Kemp et al, 2011;Schiller and Muller, 2015), JC polyomavirus (Ray et al, 2015), BK polyomavirus (Pastrana et al, 2013) etc. Many others that cannot self-assemble, or those where the viral capsid is encased inside a lipid envelope, or those where the viral surface proteins are relatively mobile/ not rigid, can also potentially be displayed in a more rigid and thermodynamically stable fashion as synthetic VLPs.…”

A comparative study of two different assay kits for the detection of secreted alkaline phosphatase in HPV antibody neutralization assays

“…In our previous studies, we used GE to conduct SEAP assay to measure HPV neutralizing antibody titers. 26,29,35 To determine if ZiVa could be an alternative to GE in clinical studies, we evaluated whether the neutralization titers measured by ZiVa correlate to those measured by GE. For this, we used culture supernatants from 293TT cell-based neutralization assays that were performed for the a The information is based on those indicated in the production sheets or certificate of analysis, or on the website of each company.…”

“…As such, cell-based in vitro neutralization assay is an ideal system to measure the levels of biologically active antibodies in clinical samples. Although different neutralization assays have been reported for HPV, [16][17][18][19][20][21][22][23][24][25] our laboratory has adopted, optimized, and validated [26][27][28][29] a pseudovirion (PsV)-based HPV neutralization assay that was originally reported by Pastrana et al 30 In this assay system, PsV particles that are composed of L1 and L2 capsid proteins from a particular HPV type are used to infect 293TT cells for 72 hr. Because a PsV particle encapsidates a reporter gene during its production, 31,32 magnitude of PsV entry and infection can be measured through the detection of the reporter gene product.…”