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A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins.

ABSTRACT: Despite an efficacious prophylactic human papillomavirus (HPV) vaccine there is still a considerable global burden of HPV-related disease. Therapeutic vaccines that could prevent cancers in at-risk women are urgently needed. Most candidate therapeutic vaccines have focused on two high-risk (hr) HPV genotypes, 16 and 18, and two viral targets, E6 and E7, which may limit global coverage and efficacy. We designed the synthetic gene '5GHPV3' by selecting conserved regions from each of the six early proteins and generating consensus sequences to represent five hrHPV genotypes. 5GHPV3 was delivered by plasmid DNA, chimpanzee adenovirus (ChAdOx1) and modified vaccinia Ankara (MVA) vectors in prime-boost regimens to mice. ChAdOx1-5GHPV3 / MVA-5GHPV3 induced higher magnitude and more durable HPV-specific T cell responses than other regimens. Vaccine-induced T cells were polyfunctional and persisted at high frequencies for at least six weeks. Importantly, HPV-specific effector CD8?+?T cells were detected in the cervix following systemic administration of ChAdOx1-5GHPV3 / MVA-5GHPV3 and increased in frequency over time, indicating continued trafficking of T cells to the cervix. Finally, T cells specific for 5GHPV3 encoded antigens were detected by IFN-? Elispot in women with current or past hrHPV infections, confirming the presence of epitopes relevant to natural immune control.

SUBMITTER: Hancock G

PROVIDER: S-EPMC6904585 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins.

Hancock Gemma G Blight Joshua J Lopez-Camacho Cesar C Kopycinski Jakub J Pocock Mamatha M Byrne Wendy W Price Michael J MJ Kemlo Phillip P Evans Ranoromanana Ionitiana RI Bloss Angela A Saunders Kathryn K Kirton Richard R Andersson Monique M Hellner Karin K Reyes-Sandoval Arturo A Dorrell Lucy L

Scientific reports 20191210 1

Despite an efficacious prophylactic human papillomavirus (HPV) vaccine there is still a considerable global burden of HPV-related disease. Therapeutic vaccines that could prevent cancers in at-risk women are urgently needed. Most candidate therapeutic vaccines have focused on two high-risk (hr) HPV genotypes, 16 and 18, and two viral targets, E6 and E7, which may limit global coverage and efficacy. We designed the synthetic gene '5GHPV3' by selecting conserved regions from each of the six early ...[more]

PMID: 31822717

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Project description:Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Dataset Information

A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins.

Publications

A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins.

Similar Datasets

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