Duration of Cellular and Humoral Responses after Quadrivalent Human Papillomavirus Vaccination in Healthy Female Adults with or without Prior Type 16 and/or 18 Exposure
Lilin Lai,
Kevin Ault,
Nadine Rouphael,
Allison Beck,
Briyana Domjahn,
Yongxian Xu,
Evan J. Anderson,
Andrew Cheng,
Aya Nakamura,
Rebecca J. Hoagland,
Colleen Kelley,
Srilatha Edupuganti,
Karen Mask,
Mirjana Nesin,
Elizabeth R. Unger,
Gitika Panicker,
Hagit David,
Mark J. Mulligan
Affiliations
Lilin Lai
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Kevin Ault
Department of Obstetrics and Gynecology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA
Nadine Rouphael
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Allison Beck
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Briyana Domjahn
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Yongxian Xu
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Evan J. Anderson
Department of Pediatrics, Emory University School of Medicine, 2015 Uppergate Drive NE, Atlanta, GA 30322, USA
Andrew Cheng
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Aya Nakamura
The EMMES Company, LLC, 401 N. Washington St., Suite 700, Rockville, MD 20850, USA
Rebecca J. Hoagland
Cota Enterprises, 16570 46th Street, McLouth, KS 66054, USA
Colleen Kelley
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Srilatha Edupuganti
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Karen Mask
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Mirjana Nesin
Division of Microbiology and Infectious Diseases, NIAID, NIH, 5601 Fishers Lane, Rockville, MD 20892-9825, USA
Elizabeth R. Unger
Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30329, USA
Gitika Panicker
Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30329, USA
Hagit David
Division of Microbiology and Infectious Diseases, NIAID, NIH, 5601 Fishers Lane, Rockville, MD 20892-9825, USA
Mark J. Mulligan
The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 500 Irvin Court Suite 200, Decatur, GA 30030, USA
Human papillomavirus virus (HPV) vaccines aim to provide durable protection and are ideal to study the association of cellular with humoral responses. We assessed the duration and characteristics of immune responses provided by the quadrivalent HPV (4vHPV) vaccine in healthy female adults with or without prior exposure with type 16 and 18 HPV. In a prospective cohort, vaccine naïve females received three doses of 4vHPV vaccine and were followed for two years to assess cellular (intracellular cytokine staining, proliferation and B cell ELISpot assays) and humoral (multiplex L1/L2 viral-like particles (VLP) and M4 ELISAs) responses. Frequencies of vaccine-specific CD4+ T cells correlated with antibody responses. Higher HPV antibody titers were found at all time points in participants previously exposed to HPV, except for anti-HPV-18 at Day 187 (one week post the third vaccination). Retrospective cohorts enrolled females who had previously received two or three 4vHPV doses and tested antibody titers by M4 ELISA and pseudovirion neutralization assay along with memory B cells (MBCs). Almost all women enrolled in a retrospective cohort with two prior doses and all women enrolled in a retrospective cohort with three prior doses had sustained antibody and memory responses. Our findings indicate that HPV vaccination induces a long-lasting, robust cellular and humoral immune responses.
