Adeno-associated viruses (AAV) have been developed and evaluated as recombinant vectors for gene therapy in many preclinical studies, as well as in clinical trials. However, only a few approaches have used recombinant AAV (rAAV) to deliver vaccine antigens. We generated an rAAV encoding the major capsid protein L1 (L1h) from the human papillomavirus type 16 (HPV16), aiming to develop a prophylactic vaccine against HPV16 infections, which are the major cause of cervical cancer in women worldwide. A single dose of rAAV5 L1h administered intranasally was sufficient to induce high titers of L1-specific serum antibodies, as well as mucosal antibodies in vaginal washes. Seroconversion was maintained for at least 1 year. In addition, a cellular immune response was still detectable 60 weeks after immunization. Furthermore, lyophilized rAAV5 L1h successfully evoked a systemic and mucosal immune response in mice. These data clearly show the efficacy of a single-dose intranasal immunization against HPV16 based on the recombinant rAAV5L1h vector without the need of an adjuvant.Genital infections with human papillomaviruses (HPV) are among the most common viral sexually transmitted infections in humans. It has been estimated that at least 50% of sexually active adults had a genital HPV infection. More than 120 different genotypes have been described thus far, 15 of which (i.e., HPV type 16 [HPV16] and HPV18) were identified as causative agents of at least 90% of cancers of the cervix and were also linked to more than the half of other anogenital cancers. Cervical cancer is the second most frequent malignant tumor in women worldwide (for a review, see reference 74).Several vaccination models against HPV have been evaluated aiming to generate neutralizing antibodies.
Background Some studies have shown an attenuated immune response in hemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against SARS-CoV-2 in a large population of hemodialysis patients from different outpatient dialysis centers. Methods We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) three to six weeks after the second mRNA vaccine dose in 179 maintenance hemodialysis and 70 non-dialysis patients (control cohort). Differences in Anti-SARS CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous COVID-19 infection, systemic immunosuppressive therapy and time on dialysis. Results We found a favorable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison to a non-dialysis cohort (median 253.5 vs. 1756 U/ml, p < 0.001). In multivariate analysis previous COVID-19 infection (p < 0.001) and female gender were associated with a significantly higher vaccine response (p 0.006) in hemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (p < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in hemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection. Conclusion We strongly argue in favor of regular antibody testing after COVID-19 vaccination in hemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.
Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.