TY - JOUR
T1 - Incorporation of RG1 epitope into HPV16L1-VLP does not compromise L1-specific immunity
AU - Schellenbacher, C.
AU - Huber, B.
AU - Skoll, M.
AU - Shafti-Keramat, S.
AU - Roden, R. B.S.
AU - Kirnbauer, R.
N1 - Funding Information:
Based on these promising preclinical results, RG1-VLP is currently produced under cGMP for a planned first-in-human clinical trial (supported by the US NCI PREVENT program). An outstanding feature of RG1-VLP, when compared to other L2-based vaccine approaches, is the very close resemblance with wild-type HPV16L1-VLP contained in licensed vaccines, suggesting a similar safety profile when using similar antigen/adjuvant doses. To support a planned phase I clinical study in humans the herein presented dose-finding study was performed to initially evaluate (a) efficacy of RG1-VLP vaccine compared to wild-type HPV16 VLP in raising HPV16L1-specific antibodies, (b) dose-dependency of cross-neutralizing L2 antibodies induced by RG1-VLP, (c) a possible use of RG1-VLP in a 2 dose vaccination regime, and (d) a bivalent RG1-VLP + 18L1-VLP vaccine formulation. All questions were to be answered in the setting of adjuvant formulations and doses applicable in humans. This vaccine study presents earliest and descriptive data from a limited number of animals on the questions addressed.
Funding Information:
This publication was supported in part by US Public Health Service grants (grants.nih.gov) from the National Cancer Institute of the National Institutes of Health under awards numbered R01CA118790, P50CA098252, and R01CA233486 to RBSR. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Further support was provided by EU-funded InfectEra: HPV-MOTIVA to RK.
Funding Information:
This publication was supported in part by US Public Health Service grants (grants.nih.gov) from the National Cancer Institute of the National Institutes of Health under awards numbered R01CA118790 , P50CA098252 , and R01CA233486 to RBSR. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Further support was provided by EU-funded InfectEra: HPV-MOTIVA to RK.
Publisher Copyright:
© 2019
PY - 2019/6/12
Y1 - 2019/6/12
N2 - The candidate pan-Human Papillomavirus (HPV) vaccine RG1-VLP are HPV16 major capsid protein L1 virus-like-particles (VLP) comprising a type-common epitope of HPV16 minor capsid protein L2 (RG1; aa17-36). Vaccinations have previously demonstrated efficacy against genital high-risk (hr), low-risk (lr) and cutaneous HPV. To compare RG1-VLP to licensed vaccines, rabbits (n = 3) were immunized thrice with 1 µg, 5 µg, 25 µg, or 125 µg of RG1-VLP or a 1/4 dose of Cervarix®. 5 µg of RG1-VLP or 16L1-VLP (Cervarix) induced comparable HPV16 capsid-reactive and neutralizing antibodies titers (62,500/12,500–62,500 or 1000/10,000). 25 µg RG1-VLP induced robust cross-neutralization titers (50–1000) against hrHPV18/31/33/45/52/58/26/70. To mimic reduced immunization schedules in adolescents, mice (n = 10) were immunized twice with RG1-VLP (5 µg) plus 18L1-VLP (5 µg). HPV16 neutralization (titers of 10,000) similar to Cervarix and Gardasil and cross-protection against hrHPV58 vaginal challenge was observed. RG1-VLP vaccination induces hrHPV16 neutralization comparable to similar doses of licensed vaccines, plus cross-neutralization to heterologous hrHPV even when combined with HPV18L1-VLP.
AB - The candidate pan-Human Papillomavirus (HPV) vaccine RG1-VLP are HPV16 major capsid protein L1 virus-like-particles (VLP) comprising a type-common epitope of HPV16 minor capsid protein L2 (RG1; aa17-36). Vaccinations have previously demonstrated efficacy against genital high-risk (hr), low-risk (lr) and cutaneous HPV. To compare RG1-VLP to licensed vaccines, rabbits (n = 3) were immunized thrice with 1 µg, 5 µg, 25 µg, or 125 µg of RG1-VLP or a 1/4 dose of Cervarix®. 5 µg of RG1-VLP or 16L1-VLP (Cervarix) induced comparable HPV16 capsid-reactive and neutralizing antibodies titers (62,500/12,500–62,500 or 1000/10,000). 25 µg RG1-VLP induced robust cross-neutralization titers (50–1000) against hrHPV18/31/33/45/52/58/26/70. To mimic reduced immunization schedules in adolescents, mice (n = 10) were immunized twice with RG1-VLP (5 µg) plus 18L1-VLP (5 µg). HPV16 neutralization (titers of 10,000) similar to Cervarix and Gardasil and cross-protection against hrHPV58 vaginal challenge was observed. RG1-VLP vaccination induces hrHPV16 neutralization comparable to similar doses of licensed vaccines, plus cross-neutralization to heterologous hrHPV even when combined with HPV18L1-VLP.
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U2 - 10.1016/j.vaccine.2019.05.011
DO - 10.1016/j.vaccine.2019.05.011
M3 - Article
C2 - 31147274
AN - SCOPUS:85066072529
SN - 0264-410X
VL - 37
SP - 3529
EP - 3534
JO - Vaccine
JF - Vaccine
IS - 27
ER -