Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine

Zheng Quan Toh; Kathleen Wen Bei Cheow; Fiona M Russell; Edwin Hoe; Rita Reyburn; James Fong; Evelyn Tuivaga; Felisita T Ratu; Cattram D Nguyen; Silivia Matanitobua; Andrea Reitsma; Sepehr N Tabrizi; Suzanne M Garland; Edward K Mulholland; Paul V Licciardi

doi:10.1093/ofid/ofy147

Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine

Open Forum Infect Dis. 2018 Jun 20;5(7):ofy147. doi: 10.1093/ofid/ofy147. eCollection 2018 Jul.

Authors

Zheng Quan Toh¹, Kathleen Wen Bei Cheow¹, Fiona M Russell^{1

2}, Edwin Hoe¹, Rita Reyburn¹, James Fong³, Evelyn Tuivaga³, Felisita T Ratu³, Cattram D Nguyen^{1

2}, Silivia Matanitobua³, Andrea Reitsma¹, Sepehr N Tabrizi^{4

5}, Suzanne M Garland^{4

5}, Edward K Mulholland^{1

6

7}, Paul V Licciardi^{1

2}

Affiliations

¹ Murdoch Children's Research Institute, Parkville, Victoria, Australia.
² Centre for International Child Health, Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
³ Ministry of Health and Medical Services, Suva, Fiji.
⁴ Department of Obstetrics and Gynecology, The University of Melbourne, The Royal Women's Hospital and Murdoch Children's Research Institute, Parkville, Victoria, Australia.
⁵ Regional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Disease, The Royal Women's Hospital, Parkville, Victoria, Australia.
⁶ London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
⁷ Department of Child Health, Menzies School of Health Research, Darwin, Northern Territory, Australia.

Abstract

Background: This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV).

Methods: A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15-19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants.

Results: Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients.

Conclusions: These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high-disease burden settings.

Keywords: adolescents; cellular immune responses; human papillomavirus vaccine; immune memory; reduced doses.