Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine

• Published in: Vaccine Vol. 25; no. 26; pp. 4931 - 4939
• Main Authors: Olsson, Sven-Eric, Villa, Luisa L., Costa, Ronaldo L.R., Petta, Carlos A., Andrade, Rosires P., Malm, Christian, Iversen, Ole-Erik, Høye, John, Steinwall, Margareta, Riis-Johannessen, Grete, Andersson-Ellstrom, Agneta, Elfgren, Kristina, von Krogh, Geo, Lehtinen, Matti, Paavonen, Jorma, Tamms, Gretchen M., Giacoletti, Katherine, Lupinacci, Lisa, Esser, Mark T., Vuocolo, Scott C., Saah, Alfred J., Barr, Eliav
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2007; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Allergy and Immunology; antibodies; Antibodies, Viral - blood; Antigens; Applied microbiology; b surface-antigen; Biological and medical sciences; Biomedical research; Birth control; cancer; cervical; Cervical cancer; Cervical intraepithelial neoplasia (CIN); Clinical Medicine; Clinical trial; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Genital warts; Gynaecology, Obstetrics and Reproductive Medicine; Gynekologi, obstetrik och reproduktionsmedicin; Health promotion; Hepatitis; hepatitis-b; Human papillomavirus; Human papillomavirus 11 - immunology; Human papillomavirus 16 - immunology; Human papillomavirus 18 - immunology; Human viral diseases; human-papillomavirus-16; Humans; Immunization Schedule; immunogenicity; Immunologi inom det medicinska området; Immunologic Memory - immunology; Immunology in the Medical Area; Infections; Infectious diseases; Klinisk medicin; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Microbiology; Miscellaneous; neutralizing epitopes; Obstetrics, Gynecology and Reproductive Medicine; Papillomavirus Infections - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - immunology; Prophylactic vaccine; Public health; Reproduktionsmedicin och gynekologi; responses; trial; Tumors; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Veterinary Science; Veterinärmedicin; Viral diseases; Viral diseases of the genital and urinary system; Virology; Virus-like particles; Womens health; Prophylactic vaccine; Genital warts; Human papillomavirus; Cervical intraepithelial neoplasia (CIN); Clinical trial; Virus-like particles; Cervical cancer; Papovaviridae; Human papillomavirus 18; Papillomavirus; Prevention; Human papillomavirus 16; Cervical intraepithelial neoplasia; Premalignant lesion; Virus like particle; Human papillomavirus 6; Vaccine; Malignant tumor; Female genital diseases; Infection; Virus; Sexually transmitted disease; Viral disease; Condyloma acuminatum; Uterine cervix diseases
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2007.03.049

The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. A total of 552, 16–23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years’ follow-up. A subset of 241 subjects ( n = 114 in the quadrivalent HPV vaccine group and n = 127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.