In Vivo Mechanisms of Vaccine-Induced Protection against HPV Infection

Laboratory of Cellular Oncology, National Cancer Institute/National Institutes of Health, Bethesda, MD 20892, USA.
Cell host & microbe (Impact Factor: 12.19). 09/2010; 8(3):260-70. DOI: 10.1016/j.chom.2010.08.003
Source: PubMed

ABSTRACT Using a human papillomavirus (HPV) cervicovaginal murine challenge model, we microscopically examined the in vivo mechanisms of L1 virus-like particle (VLP) and L2 vaccine-induced inhibition of infection. In vivo HPV infection requires an initial association with the acellular basement membrane (BM) to induce conformational changes in the virion that permit its association with the keratinocyte cell surface. By passive transfer of immune serum, we determined that anti-L1 antibodies can interfere with infection at two stages. Similarly to active VLP immunization, transfer of high L1 antibody concentrations prevented BM binding. However, in the presence of low concentrations of anti-L1, virions associated with the BM, but to the epithelial cell surface was not detected. Regardless of the concentration, L2 vaccine-induced antibodies allow BM association but prevent association with the cell surface. Thus, we have revealed distinct mechanisms of vaccine-induced inhibition of virus infection in vivo.

Download full-text


Available from: Patricia M Day, Jul 07, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models, and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine.
    Cell host & microbe 10/2012; 12(4):396-407. DOI:10.1016/j.chom.2012.09.008 · 12.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is unclear what level of neutralizing antibody is sufficient to protect cattle from experimental bovine papillomavirus type 4 (BPV4) challenge. Markedly lower, and often undetected, serum neutralizing antibody titers were associated with protection in cattle vaccinated with BPV4 L2 as compared to L1 VLP. We hypothesized that vaccination with concatemers of the N-terminal protective epitopes of L2 derived from multiple animal papillomavirus types would enhance the breadth and strength of immunity. Therefore we generated a multimeric L2 antigen derived from three bovine and three canine papillomavirus types with divergent phenotypes and purified it from bacteria. Mice vaccinated three times with this six type L2 vaccine formulated in alum or RIBI adjuvant generated robust serum neutralizing antibody titers against BPV1, BPV4 and canine oral papillomavirus (COPV). Furthermore, vaccination with this six type L2 vaccine formulated in adjuvant, like BPV1 L1 VLP, protected the mice from experimental challenge with BPV1 pseudovirus.
    Virology 09/2011; 420(1):43-50. DOI:10.1016/j.virol.2011.07.020 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The paper presents a priority-driven concurrency control protocol to schedule active transactions accessing distributed real-time databases based on priority information. This protocol controls real-time transactions with different priority more effectively. By combining flexible synchronization techniques for desirable real-time conflict resolution, it intends to avoid unnecessary aborts or blocking of conflicting transactions. Thus, flexible priority-driven scheduling enables this protocol to interleave and complete as many transactions as possible without sacrificing data or timing constraints. Performance is achieved by increasing the number of transactions, especially with higher priority
    TENCON '93. Proceedings. Computer, Communication, Control and Power Engineering.1993 IEEE Region 10 Conference on; 11/1993