Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity.

2.50
Hdl Handle:
http://hdl.handle.net/10541/69793
Title:
Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity.
Authors:
Karanam, Balasubramanyam; Gambhira, Ratish; Peng, Shiwen; Jagu, Subhashini; Kim, Dae-Jin; Ketner, Gary W; Stern, Peter L; Adams, Robert J; Roden, Richard B S
Abstract:
A vaccine comprising human papillomavirus type 16 (HPV16) L2, E6 and E7 in a single tandem fusion protein (termed TA-CIN) has the potential advantages of both broad cross-protection against HPV transmission through induction of L2 antibodies able to cross neutralize different HPV types and of therapy by stimulating T cell responses targeting HPV16 early proteins. However, patients vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7-specific T cell responses. Here we test TA-CIN formulated along with the adjuvant GPI-0100, a semi-synthetic quillaja saponin analog that was developed to promote both humoral and cellular immune responses. Subcutaneous administration to mice of TA-CIN (20 microg) with 50microg GPI-0100, three times at biweekly intervals, elicited high titer HPV16 neutralizing serum antibody, robust neutralizing titers for other HPV16-related types, including HPV31 and HPV58, and neutralized to a lesser extent other genital mucosatropic papillomaviruses like HPV18, HPV45, HPV6 and HPV11. Notably, vaccination with TA-CIN in GPI-0100 protected mice from cutaneous HPV16 challenge as effectively as HPV16 L1 VLP without adjuvant. Formulation of TA-CIN with GPI-0100 enhanced the production of E7-specific, interferon gamma producing CD8(+) T cell precursors by 20-fold. Vaccination with TA-CIN in GPI-0100 also completely prevented tumor growth after challenge with 5x10(4) HPV16-transformed TC-1 tumor cells, whereas vaccination with TA-CIN alone delayed tumor growth. Furthermore, three monthly vaccinations with 125 microg of TA-CIN and 1000 microg GPI-0100 were well tolerated by pigtail macaques and induced both HPV16 E6/E7-specific T cell responses and serum antibodies that neutralized all HPV types tested.
Affiliation:
Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.
Citation:
Vaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity. 2009, 27 (7):1040-9 Vaccine
Journal:
Vaccine
Issue Date:
11-Feb-2009
URI:
http://hdl.handle.net/10541/69793
DOI:
10.1016/j.vaccine.2008.11.099
PubMed ID:
19095032
Type:
Article
Language:
en
ISSN:
0264-410X
Appears in Collections:
All Paterson Institute for Cancer Research; Immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorKaranam, Balasubramanyam-
dc.contributor.authorGambhira, Ratish-
dc.contributor.authorPeng, Shiwen-
dc.contributor.authorJagu, Subhashini-
dc.contributor.authorKim, Dae-Jin-
dc.contributor.authorKetner, Gary W-
dc.contributor.authorStern, Peter L-
dc.contributor.authorAdams, Robert J-
dc.contributor.authorRoden, Richard B S-
dc.date.accessioned2009-06-05T10:30:20Z-
dc.date.available2009-06-05T10:30:20Z-
dc.date.issued2009-02-11-
dc.identifier.citationVaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity. 2009, 27 (7):1040-9 Vaccineen
dc.identifier.issn0264-410X-
dc.identifier.pmid19095032-
dc.identifier.doi10.1016/j.vaccine.2008.11.099-
dc.identifier.urihttp://hdl.handle.net/10541/69793-
dc.description.abstractA vaccine comprising human papillomavirus type 16 (HPV16) L2, E6 and E7 in a single tandem fusion protein (termed TA-CIN) has the potential advantages of both broad cross-protection against HPV transmission through induction of L2 antibodies able to cross neutralize different HPV types and of therapy by stimulating T cell responses targeting HPV16 early proteins. However, patients vaccinated with TA-CIN alone develop weak HPV neutralizing antibody and E6/E7-specific T cell responses. Here we test TA-CIN formulated along with the adjuvant GPI-0100, a semi-synthetic quillaja saponin analog that was developed to promote both humoral and cellular immune responses. Subcutaneous administration to mice of TA-CIN (20 microg) with 50microg GPI-0100, three times at biweekly intervals, elicited high titer HPV16 neutralizing serum antibody, robust neutralizing titers for other HPV16-related types, including HPV31 and HPV58, and neutralized to a lesser extent other genital mucosatropic papillomaviruses like HPV18, HPV45, HPV6 and HPV11. Notably, vaccination with TA-CIN in GPI-0100 protected mice from cutaneous HPV16 challenge as effectively as HPV16 L1 VLP without adjuvant. Formulation of TA-CIN with GPI-0100 enhanced the production of E7-specific, interferon gamma producing CD8(+) T cell precursors by 20-fold. Vaccination with TA-CIN in GPI-0100 also completely prevented tumor growth after challenge with 5x10(4) HPV16-transformed TC-1 tumor cells, whereas vaccination with TA-CIN alone delayed tumor growth. Furthermore, three monthly vaccinations with 125 microg of TA-CIN and 1000 microg GPI-0100 were well tolerated by pigtail macaques and induced both HPV16 E6/E7-specific T cell responses and serum antibodies that neutralized all HPV types tested.en
dc.language.isoenen
dc.subject.meshAdjuvants, Immunologic-
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Viral-
dc.subject.meshCD8-Positive T-Lymphocytes-
dc.subject.meshCapsid Proteins-
dc.subject.meshCytokines-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunization, Secondary-
dc.subject.meshInjections, Subcutaneous-
dc.subject.meshMacaca-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshNeutralization Tests-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshPapillomavirus Vaccines-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshRepressor Proteins-
dc.subject.meshSaponins-
dc.titleVaccination with HPV16 L2E6E7 fusion protein in GPI-0100 adjuvant elicits protective humoral and cell-mediated immunity.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, The Johns Hopkins University, Baltimore, MD 21231, USA.en
dc.identifier.journalVaccineen

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