Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent Human Papillomavirus (HPV) vaccine in adolescent Fijian girls, and subsequent responses to a single dose of bivalent HPV vaccine: a prospective cohort study

Toh, Zheng Quan, Russell, Fiona M., Reyburn, Rita, Fong, James, Tuivaga, Evelyn, Ratu, Tupou, Nguyen, Cattram D., Devi, Rachel, Kama, Mike, Matanitobua, Silivia, Tabrizi, Sepehr N., Garland, Suzanne M., Sinha, Rohit, Frazer, Ian, Tikoduadua, Lisi, Kado, Joseph, Rafai, Eric, Mulholland, Edward K. and Licciardi, Paul V. (2017) Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent Human Papillomavirus (HPV) vaccine in adolescent Fijian girls, and subsequent responses to a single dose of bivalent HPV vaccine: a prospective cohort study. Clinical Infectious Diseases, 64 7: 852-859. doi:10.1093/cid/ciw865


Author Toh, Zheng Quan
Russell, Fiona M.
Reyburn, Rita
Fong, James
Tuivaga, Evelyn
Ratu, Tupou
Nguyen, Cattram D.
Devi, Rachel
Kama, Mike
Matanitobua, Silivia
Tabrizi, Sepehr N.
Garland, Suzanne M.
Sinha, Rohit
Frazer, Ian
Tikoduadua, Lisi
Kado, Joseph
Rafai, Eric
Mulholland, Edward K.
Licciardi, Paul V.
Title Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent Human Papillomavirus (HPV) vaccine in adolescent Fijian girls, and subsequent responses to a single dose of bivalent HPV vaccine: a prospective cohort study
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1058-4838
1537-6591
Publication date 2017-04-01
Year available 2016
Sub-type Article (original research)
DOI 10.1093/cid/ciw865
Open Access Status Not yet assessed
Volume 64
Issue 7
Start page 852
End page 859
Total pages 8
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Subject 2726 Microbiology (medical)
2725 Infectious Diseases
Abstract Background. The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. Methods. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. Results. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Conclusions. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV.
Formatted abstract
Background: The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously.

Methods: A prospective cohort study was undertaken in 200 Fijian girls 15–19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay.

Results: After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695–2896]; 2D: 1476 [95% CI, 1019–2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396–5783]; 2D: 2951 [95% CI, 1984–4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511–4530]; 2D: 3275 [95% CI, 2452–4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445–888]; 2D: 606 [95% CI, 462–862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously.

Conclusions: Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV.
Keyword Human papillomavirus vaccine
Reduced doses
Neutralizing antibodies
Immune memory
Adolescents
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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