OC 06-10SUSTAINED ANTIBODY RESPONSES SIX YEARS FOLLOWING REDUCED DOSE QUADRIVALENT HPV VACCINE IN ADOLESCENT FIJIAN GIRLS

05. HPV prophylactic vaccines
Z.Q. Toh 1, F.M. Russell 2, R. Reyburn 1, J. Fong 3, E. Tuivaga 3, T. Ratu 3, C.D. Nguyen 1, R. Devi 3, M. Kama 3, M. Silivia 3, S.N. Tabrizi 4, S.M. Garland 4, R. Sinha 5, I. Frazer 5, L. Tikoduadua 3, J. Kado 3, E. Rafai 3, E.K. Mulholland 6, P.V. Licciardi 1.
1Murdoch Childrens Research Institute (Australia), 2Murdoch Childrens Research Institute;The University of Melbourne, Department of Paediatrics, Centre for International Child Health (Australia), 3Ministry of Health and Medical Services (Fiji), 4The Royal Women’s Hospital and Murdoch Childrens Research Institute, Department of Obstetrics and Gynecology; The Royal Women’s Hospital Regional, WHO HPV Reference Laboratory, Department of Microbiology and Infectious Disease (Australia), 5The University of Queensland Diamantina Institute (Australia), 6Murdoch Childrens Research Institute;London School of Hygiene and Tropical Medicine;Menzies School of Health Research, Department of Child Health (Australia)

Background / Objectives

Recently, the World Health Organization has recommended two dose HPV vaccine schedule separated by 6 months to girls <15 years old as an alternative to the current three dose schedules. However, the long-term protection following reduced dose schedules is unknown. This study examined long-term immunity by comparing the antibody responses in girls previously given 3 doses of 4vHPV (Gardasil®, Merck Inc.) 6-7 years ago with reduced doses (1 or 2 doses).


Methods

A prospective cohort study was undertaken in 200 Fijian girls (15-19 years old) who previously received 0, 1, 2 or 3 doses of 4vHPV 6-7 years ago (N=50/group). Blood was taken pre- and 28 days following a single dose of 2vHPV (Cervarix®, GSK), and HPV 6, 11, 16 and 18 neutralising antibodies (NAb) were measured using the pseudovirion neutralisation assay.


Results

Geometric Mean NAb Titres (GMT) were similar for HPV 16 and 18 between the 2 and 3 dose recipients: HPV 16 (3 doses: 3575; 2 doses: 2904; p=0.37); HPV 18 (3 doses: 687; 2 doses: 543; p=0.41). Single 4vHPV dose recipients had higher HPV 16 and 18 NAb titres than unvaccinated girls (HPV 16 and 18: p<0.001). Post- 2vHPV NAb titres against HPV 16 and 18 increased at least 14- and 39-fold, respectively to a level that were similar between groups previously given 1, 2 or 3 doses of 4vHPV (HPV16 GMT: 49,114-51,915; HPV 18 GMT: 22,286-29,076). Interim analysis for HPV6 and 11 showed a similar dosage effect prior to 2vHPV between the groups after 6-7 years, but with no increase in NAb titres following 2vHPV.


Conclusion

A dose-response in NAb titres was observed in girls given 1, 2 or 3 doses of 4vHPV 6-7 years previously, but there was no significant difference in NAb titres between the 2 and 3 dose groups. A single 4vHPV dose produced substantial HPV16 and 18 NAb titres that were 6- and 3-fold, respectively, higher than unvaccinated individuals after 6-7 years, suggesting a possible benefit of a single dose, although the clinical significance is unknown. Interim analysis showed no evidence of cross-neutralising antibodies against HPV 6 and 11 in all groups following a single dose of 2vHPV. Assays are being developed to determine cellular responses. This information supports the current two dose 4vHPV schedule.


References