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Infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions. A review of the literature.

ABSTRACT: BACKGROUND:Human papillomavirus (HPV) infects and propagates in the cervical mucosal epithelium. Hence, in addition to assessing systemic immunity, the accurate measurement of cervical immunity is important to evaluate local immune responses to HPV infection and vaccination. This review discusses studies that investigated the presence of infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions (CVS). METHODS:We searched the two main health sciences databases, PubMed and the ISI Web of Science, from the earliest dates available to March 2019. From the eligible publications, information was extracted regarding: (i) study design, (ii) the reported HPV-specific antibody concentrations in CVS (and the associated serum levels, when provided), (iii) the CVS collection method, and (iv) the immunoassays used. RESULTS:The systematic search and selection process yielded 44 articles. The evidence of HPV-specific antibodies in CVS after natural infection (26/44) and HPV vaccination (18/44) is discussed. Many studies indicate that HPV-specific antibody detection in CVS is variable but feasible with a variety of collection methods and immunoassays. Most CVS samples were collected by cervicovaginal washing or wicks, and antibody presence was mostly determined by VLP-based ELISAs. The moderate to strong correlation between vaccine-induced antibody levels in serum and in CVS indicates that HPV vaccines generate antibodies that transudate through the cervical mucosal epithelium. CONCLUSION:Although HPV-specific antibodies have lower titres in CVS than in serum samples, studies have shown that their detection in CVS is feasible. Nevertheless, the high variability of published observations and the lack of a strictly uniform, well-validated method for the collection, isolation and quantification of antibodies indicates a need for specific methods to improve and standardize the detection of HPV-specific antibodies in CVS.

SUBMITTER: Pattyn J

PROVIDER: S-EPMC6804463 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions. A review of the literature.

Pattyn Jade J Van Keer Severien S Tjalma Wiebren W Matheeussen Veerle V Matheeussen Veerle V Van Damme Pierre P Vorsters Alex A

Papillomavirus research (Amsterdam, Netherlands) 20190905

<h4>Background</h4>Human papillomavirus (HPV) infects and propagates in the cervical mucosal epithelium. Hence, in addition to assessing systemic immunity, the accurate measurement of cervical immunity is important to evaluate local immune responses to HPV infection and vaccination. This review discusses studies that investigated the presence of infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions (CVS).<h4>Methods</h4>We searched the two main health sciences databa ...[more]

PMID: 31494291

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Project description:Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P ≤ .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, P ≤ .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, P ≤ .0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, P ≤ .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection.

Project description:Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition.The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women.Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test.Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P?.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3?; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P?.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P?.03).Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions.

Project description:Enterobactin (Ent)-mediated high-affinity iron acquisition is critical for Gram-negative bacteria to survive in the host. Given the bacteriostatic effect of lipocalin resulting from its potent Ent-binding ability, immune intervention directly targeting Ent is promising for iron-dependent pathogen control. Recently, an Ent conjugate vaccine was reported, but it still has several significant weaknesses. In this study, we sought to develop an innovative Ent conjugate vaccine that can induce a high level of antibodies directed against Ent and to provide solid evidence demonstrating siderophore-binding capacity of Ent-specific antibodies. Using a simple method, we successfully conjugated purified Ent to different carriers, including keyhole limpet hemocyanin (KLH), bovine serum albumin, and CmeC, a vaccine candidate for Campylobacter control. Subcutaneous immunization of rabbits with the KLH-Ent conjugate triggered a strong systemic IgG immune response with an up to 16,384-fold increase in IgG titer directed against whole conjugate and an up to 4,096-fold increase in the level of specific anti-Ent IgG. To evaluate the ability of Ent-specific IgG to bind to the Ent derivatives present in vivo, various Ent derivatives were chemically synthesized and a unique enzyme-linked immunosorbent assay method was developed. The Ent-specific IgG also displayed exceptional reactivity to ferric Ent, a linear trimer of Ent, and different salmochelins. Growth assays further demonstrated that the Ent-specific antibodies significantly inhibited Ent-dependent growth of Campylobacter spp. and Escherichia coli Collectively, this study reports an efficient method to prepare a new type of Ent conjugate vaccines for inducing a high level of Ent-specific antibodies, which can bind to various Ent derivatives and display lipocalin-like bacteriostatic features.IMPORTANCE Ent-mediated high-affinity iron acquisition is a universal and critical contributor for Gram-negative pathogens to survive and infect hosts. Published information has supported an innovative immune intervention strategy that directly targets Ent to starve pathogens by limiting the availability of iron to be utilized. Compared to a recently published Ent conjugate, there are three advantages of the vaccine described in this study: ease of preparation, induction of high titer of anti-Ent IgG, and the ability of Ent-specific antibodies to bind various Ent derivatives, including the salmochelins that help enteric pathogens evade sequestration of siderophores by host lipocalins. In addition, the Ent-specific antibodies were demonstrated to function similarly to lipocalin to interfere with the Ent-dependent growth of Campylobacter and E. coli under iron-restricted conditions. This study has significant potential for broader applications to prevent and control various Gram-negative infections in humans and animals.

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Infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions. A review of the literature.

Publications

Infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions. A review of the literature.

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