Induction of cross‐neutralizing antibodies by sequential immunization with heterologous papillomavirus L1VLPs and its implications for HPV prophylactic vaccines

Abstract

Sequential immunization with antigens from different strains of HIV‐1, influenza viruses or dengue viruses induced cross‐neutralizing antibodies and enhanced the antibody responses against previous antigens. The characteristics of neutralizing antibodies induced by sequential immunization with different types of human papillomavirus (HPV) L1 virus‐like particles (L1VLPs) are unclear. In this study, mice were primed with one or two types (HPV‐16 or HPV16/18) of L1VLPs, then boosted sequentially with HPV6/18/45/11/31/58 or HPV6/45/11/31/58 L1VLPs, and sera were analyzed with HPV pseudovirus‐based neutralization assay. The results showed that neutralizing activities against earlier immunized vaccine types were enhanced gradually by subsequent immunizations, and low levels of neutralizing activities against nonvaccine types (HPV33/35/52/59/68) were also observed. After absorbing the immune sera with vaccine‐type (HPV16/18/45) L1VLPs, neutralizing activities against tested priming and boosting types (HPV16/18/58) decreased significantly, and that against nonvaccine type (HPV‐33) was also partially eliminated. Moreover, neutralizing activities against vaccine types (HPV16/58) were significantly reduced after absorbing with nonvaccine‐type VLPs (HPV33/52). These data suggest that cross‐neutralizing epitopes exist among different HPV L1VLPs. The cross‐neutralizing activities against nonvaccine types and the enhanced neutralizing activities against earlier immunized vaccine types may result from sequential boosting with these cross‐neutralizing epitopes. These observations support early vaccination with more types of L1VLPs derived from HPVs that cause a serious threat to the population.

Immunogenicity of novel DNA vaccines encoding receptor‐binding domain (RBD) dimer‐Fc fusing antigens derived from different SARS‐CoV‐2 variants of concern

“…Studies on influenza virus, HIV and HPV, etc . reported that sequential immunization with similar antigens can enhance conserved epitope‐dependent humoral and cellular immune responses 51–53 . Therefore, in this study, mice were sequentially immunized with 2RBD‐Fc, 2dRBD‐Fc, and 2omRBD‐Fc (SI group), and the characteristics of the induced humoral and cellular immune responses were assessed.…”

“…reported that sequential immunization with similar antigens can enhance conserved epitopedependent humoral and cellular immune responses. [51][52][53] Therefore, F I G U R E 4 Sera antibody responses elicited by sequential immunization with DNA vaccines derived from Wuhan-Hu-1, delta and omicron VOC. Schematic diagram of immunization schedule was shown in (A).…”

Enhancement of Neutralization Responses through Sequential Immunization of Stable Env Trimers Based on Consensus Sequences from Select Time Points by Mimicking Natural Infection

“…Sequential immunization has been used to develop vaccines against highly variable viruses, such as influenza viruses [ 32 , 33 ] and human papillomaviruses [ 34 ]. This approach has also been used for HIV-1 vaccine development, but no significant improvements have been achieved by simply using the unrelated Env immunogens from different virus strains [ 35 , 36 , 37 ].…”