Immune Response To Non-Targeted HPV Subtypes, After Varying Doses Of Quadrivalent HPV Vaccine Administration

Priya PRABHU, Rajiv Gandhi Centre for Biotechnology, India
MUWONGE R. 2 , BUTT J. 3 , MICHEL A. 3 , SEHR P. 4 , MULLER M. 3 , WATERBOER T. 3 , BHATLA N. 5 , TOMMASINO M. 2 , LUCAS E. 2 , BASU P. 2 , SANKARANARAYANAN R. 2 , PILLAI M. 1 , PAWLITA M. 3

1 Translational Cancer Research Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India
2 International Agency for Research on Cancer, Lyon, France
3 German Cancer Research Centre (DKFZ), Heidelberg,Germany
4 European Molecular Biology Laboratory(EMBL), Heidelberg, Germany
5 All India Institute of Medical Sciences (AIIMS), New Delhi, India

Purpose
Evaluation of immune-responses of quadrivalent HPV vaccine against non-targeted HPV-types. 
Methods
The cohort study carried out at 9 Indian sites enrolled unmarried girls aged 9-18 years. We compared four cohorts of girls receiving 3 doses on days 1, 60 and 180 or later (3-dose); 2 doses on days 1 and 180 or later (2-dose); 2 doses on days 1 and 60 by default (2 doses/D); and 1 dose by default (1 dose/D). The primary outcomes considered were immunogenicity demonstrated by level and avidity of L1-binding antibodies, levels of neutralizing-antibodies for non-vaccine-targeted HPV-types related to HPV-16 (papillomavirus species a9: HPV-31/33/35/45/52/58) and HPV-18 (species a7: HPV-45).
Results
 The 2-dose protocol induced high peak geometric mean immune-responses non-inferior to the 3-dose protocol at month-7 after first dose for the non-vaccine-targeted HPV-31/33/35/52/58/45. These responses in both dose groups dropped to or below seropositivity levels by the 48th month after first dose, except for HPV-31. Geometric mean immune-responses in 2 doses/D groups at month-18 after first dose were non-inferior, whereas the responses of the 1-dose/D group were inferior to  3-dose group for all 7 non-vaccine targeted HPV-types analyzed. Avidity indices above 50% were observed at month-18 after first dose in different dose groups for these 7 HPV-types except in 1-dose/D for HPV-33, and 2-dose, 2-doses/D and 1-dose/D for HPV-35. Proportion of samples with detectable concentrations of neutralizing antibodies for 3-dose, 2-dose, 2-dose/D and 1-dose/D vaccination cohorts at month-18 after first dose were 51%, 39%, 29% and 5% for HPV-31, 12%, 12%, 3% and 3% for HPV-33, 8%, 5%, 3% and 7% for HPV-45, and 2%, 0%, 0% and 2% for HPV58, respectively. 
​Conclusions
These observations need to be correlated with genital HPV DNA status and disease end-points as the immune correlates of protection are still unknown
Funding source
Bill and Melinda Gates Foundation