The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the ...recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose 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 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.
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.
Current Human papillomavirus (HPV) L1 VLP vaccines protect against HPV-16 and HPV-18-associated cancers, in females and males. Although correlates of protection have not been identified, HPV-specific ...antibodies at sites of infection are thought to be the main mechanism of protection afforded by vaccination. Oral sampling has gained increased attention as a potential alternative to serum in monitoring immunity to vaccination and understanding local immunity in oral cancers.
Serum was collected via venipuncture, and saliva was collected via oral rinses and Merocel® sponges from healthy volunteers: 16 unvaccinated females, 6 females (ages 24–41) and 6 mid-adult aged males (ages 27–45) recipients of three doses of the HPV-16/18/6/11 vaccine (Gardasil®). Mid-adult male vaccine trial participants were compared to female participants. Samples were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G levels by an L1 virus-like particle-based enzyme-linked immunosorbent assay (ELISA).
All vaccinated participants had detectable serum anti-HPV-16 and anti-HPV-18 antibodies. Optimal standard concentration range and sample serial dilutions for oral rinses were determined. The standard curve was not affected by the type of solution examined. Reproducibility of HPV-16 and HPV-18 antibody titers in mouthwash (overall CV < 10%) or in Merocel® extraction buffer was robust (CV < 13%). Excellent assay linearity (R2 > 0.9) was observed for sera spiked controls in both solutions. HPV-16 and HPV-18 specific antibodies were detectable in saliva from vaccine recipients, both in mouthwash and in Merocel® sponges but levels were several logs lower than those in serum.
This study confirms the application of HPV-16 and HPV-18 ELISAs currently used in sero-epidemiological studies of immunogenicity of HPV vaccines for use with oral samples. Oral samples may be a useful resource for the detection of HPV-16 and HPV-18-specific antibodies in saliva following vaccination.
The Coronavirus disease 2019 (COVID-19) pandemic presented the scientific community with an immediate need for accurate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology assays, ...resulting in an expansion of assay development, some without following a rigorous quality control and validation, and with a wide range of performance characteristics. Vast amounts of data have been gathered on SARS-CoV-2 antibody response; however, performance and ability to compare the results have been challenging. This study seeks to analyze the reliability, sensitivity, specificity, and reproducibility of a set of widely used commercial, in-house, and neutralization serology assays, as well as provide evidence for the feasibility of using the World Health Organization (WHO) International Standard (IS) as a harmonization tool. This study also seeks to demonstrate that binding immunoassays may serve as a practical alternative for the serological study of large sample sets in lieu of expensive, complex, and less reproducible neutralization assays. In this study, commercial assays demonstrated the highest specificity, while in-house assays excelled in antibody sensitivity. As expected, neutralization assays demonstrated high levels of variability but overall good correlations with binding immunoassays, suggesting that binding may be reasonably accurate as well as practical for the study of SARS-CoV-2 serology. All three assay types performed well after WHO IS standardization. The results of this study demonstrate there are high performing serology assays available to the scientific community to rigorously dissect antibody responses to infection and vaccination.
Previous studies have shown significant variability in SARS-CoV-2 antibody serology assays, highlighting the need for evaluation and comparison of these assays using the same set of samples covering a wide range of antibody responses induced by infection or vaccination. This study demonstrated that there are high performing assays that can be used reliably to evaluate immune responses to SARS-CoV-2 in the context of infection and vaccination. This study also demonstrated the feasibility of harmonizing these assays against the International Standard and provided evidence that the binding immunoassays may have high enough correlation with the neutralization assays to serve as a practical proxy. These results represent an important step in standardizing and harmonizing the many different serological assays used to evaluate COVID-19 immune responses in the population.
Highlights ► Evaluated kinetics of Cervarix® -induced neutralization and avidity antibodies. ► Evaluated effects of homologous HPV infection on Cervarix® -induced antibody levels. ► 3 doses of ...Cervarix® induces significant levels of vaccine-related HPV antibodies. ► HPV-16 avidity has similar kinetic profile as neutralizing antibodies. ► Following 3 doses of Cervarix® , HPV infection had little effect on antibody levels.
Highlights • One or two dose HPV vaccine immunogenicity in girls 36 months after last dose did not meet non-inferiority thresholds. • However, antibody levels generated were similar to those in adult ...female populations where efficacy is established. • If a two-dose regimen is sufficient for protection, low-resource settings may have lower costs and easier vaccine delivery.
Highlights • Patients with Fanconi anemia (FA) are at very high risk for head and neck and gynecologic. • Squamous cell carcinomas. • We measured HPV L1 antibodies in unvaccinated and vaccinated ...patients with Fanconi anemia. • Antibody levels unvaccinated FA patients were in the reported range for unvaccinated healthy women. • Post-vaccination levels were in the reported range for vaccinated healthy women. • Post-vaccination levels remained elevated for up to five years.
Abstract Human papillomavirus (HPV)-specific antibodies are proposed to be the correlate of protection afforded by HPV L1 virus-like particle (VLP) vaccines. Previous studies have characterized the ...systemic antibody response to immunization in terms of both the quantity and the ability to neutralize HPV. Here, we have adapted a generalized memory B cell ELISPOT to the HPV16 system and expanded the analysis of the systemic antibody response to include an avidity measurement of HPV L1 VLP-specific antibodies. We show the results of the memory B cell ELISPOT significantly correlated with IgG and neutralizing antibody titers, but not with the avidity measurement. This is the first comprehensive study to correlate a variety of humoral aspects potentially associated with protective immunity following vaccination with a HPV16 L1 VLP vaccine.
Abstract Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized ...dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the significance of a rare missense variant in the Tor1a gene (c. 613T > A, p. F205I), previously identified in a patient with sporadic late-onset focal dystonia, by modeling it in mice. Homozygous F205I mice have motor impairment, reduced steady-state levels of TorsinA, altered corticostriatal synaptic plasticity, and prominent brain imaging abnormalities in areas associated with motor function. Thus, the F205I variant causes abnormalities in domains affected in people and/or mouse models with the DYT1 Tor1a mutation (ΔE). Our findings establish the pathological significance of the F205I Tor1a variant and provide a model with both etiological and phenotypic relevance to further investigate dystonia mechanisms.
Background. Human papillomavirus virus type 16 (HPV-16) and HPV-18 cause a large proportion of oropharyngeal cancers, which are increasing in incidence among males, and vaccine efficacy against oral ...HPV infections in men has not been previously evaluated. Methods. Sera and saliva collected in mouth wash and Merocel sponges at day 1 and month 7 were obtained from 150 men aged 27-45 years from Tampa, Florida, and Cuernavaca, Mexico, who received Gardasil at day 1 and months 2 and 6. Specimens were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G (IgG) levels by an LI virus-like particle-based enzyme-linked immunosorbent assay. Results. All participants developed detectable serum anti-HPV-16 and anti-HPV-18 antibodies, and most had detectable antibodies in both oral specimen types at month 7 (HPV-16 was detected in 93.2% of mouthwash specimens and 95.7% of sponge specimens; HPV-18 was detected in 72.1% and 65.5%, respectively). Antibody concentrations in saliva were approximately 3 logs lower than in serum. HPV-16-and HPV-18-specific antibody levels, normalized to total IgG levels, in both oral specimen types at month 7 were significantly correlated with serum levels (for HPV-16, p was 0.90 for mouthwash specimens and 0.92 for sponge specimens; for HPV-18, p was 0.89 and 0.86, respectively). Conclusions. This is the first study demonstrating that vaccination of males with Gardasil induces HPV antibody levels at the oral cavity that correlate with circulating levels.
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