Initially, there is a rapid decline, as short-lived antibody-secreting cells expire, followed by a gradual decline or plateauing in levels, with the antibodies predominantly produced by long-lived plasma cells in the bone marrow. group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 Z-FA-FMK times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection. Introduction In a community-based phase III trial of Cervarix in young Costa Rican women, we recently reported that, unexpectedly, the efficacy of two or even a single dose was similar to that of three doses in preventing persistent HPV16/18 infection over 4 years (1). Vaccination with two or even one vaccine dose could simplify the logistics and reduce the cost of vaccination in the developing world, where more than 85% of cervical cancers occur and it is the most common cause of cancer-related death in women (2, 3). While we observed high vaccine efficacy among those who received one vaccine dose for 4 years, it is not known whether this protection was despite antibody titers that waned over time or whether antibody levels stabilized during follow-up. Addressing this question helps to determine whether the virus-like particle (VLP) vaccine behaves more like live attenuated vaccines, which often confer long-term protection, or simple protein vaccines, which require periodic boosting. Most antiviral prophylactic vaccines are thought to function primarily by inducing virus-neutralizing antibodies (4). Antibody responses to vaccination, or to infections that clear, generally have a biphasic decline from their peak (5). Initially, there is a rapid decline, as short-lived antibody-secreting cells expire, followed by a gradual decline or plateauing in levels, with the antibodies predominantly produced by long-lived plasma cells in the bone marrow. The rate of decline during the second phase varies greatly across vaccines. Antibody titers induced by live-attenuated virus vaccines, for example, measles and mumps, tend to be very durable, despite being administered in one, or at most, two doses (6). In contrast, the half-lives of the antibody titers induced by simple protein-subunit vaccines, for example, tetanus and diphtheria, are Z-FA-FMK much shorter, despite the routine administration of multiple doses. Consequently, multiple initial doses and periodic boosters are generally recommended for most protein-subunit vaccines, with profound effects on the cost of vaccination programs. The ordered, repetitive, and dense display of epitopes on a virion surface is believed to induce exceptionally strong antibody responses. The commercial HPV prophylactic vaccines provide an opportunity to evaluate in humans the durability of the antibody response to virus-like displayed foreign antigens in the absence of infection because they are based on noninfectious VLPs with an ordered array of 72 pentamers of the L1 major capsid protein that structurally and antigenically mimics the surface of authentic virions (7). In phase III clinical trials, both Cervarix, a bivalent vaccine which contains HPV16 and HPV18 VLPs, and Gardasil, a quadrivalent one which contains HPV6, HPV11, HPV16, and HPV18 VLPs, induced durable antibody responses and strong protection from Z-FA-FMK infection and anogenital neoplastic diseases by the vaccine-targeted types after administration of the recommended Z-FA-FMK three doses over 6 months (8). After three doses, the geometric mean antibody titers (GMT) for Cervarix were shown to be essentially stable between years 2 and 8.4, the longest reported follow-up Rabbit Polyclonal to PEX3 (9), supporting the conjecture that antigen structure might be more critical than active infection for inducing a durable antibody response. However, it remains unclear whether two doses, or a single priming dose, of a VLP vaccine is sufficient to induce an antibody response that stabilizes over time. Here, we investigated the immunogenicity of Cervarix among women from The Costa Rica Z-FA-FMK HPV16/18 Vaccine Trial (CVT) who received one or two vaccine doses to those who received the full three-dose schedule and to antibody levels among unvaccinated women who were seropositive at enrollment (before vaccination) presumably from natural infection. Using a VLP-based ELISA and an neutralization assay, we analyzed the serum.