Effectiveness and B-memory Cell Response to QHPV Vaccine 9-years Post-vaccination Among HIV-infected Boys and Girls

HPV-Related Carcinoma Clinical Trial

Official title:

Effectiveness of the QHPV Among Kenyan HIV Infected Girls and Boys 9 Years Post Vaccination

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04920526
• Other study ID #: MISP 60583
• Status: Not yet recruiting
• Start date: August 2021
• Est. completion date: December 2022

Study information

• Verified date: June 2021
• Source: Kenya Medical Research Institute
• Contact: Nelly Mugo, MD
• Phone: 254733629665
• Email: rwamba[@]uw.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In 2013, the Investigators enrolled a cohort of 180 HIV-1 infected adolescent girls and boys ages 9-14 years and administered three doses of the QHPV vaccine (NCT04711265). For this study, the Investigators shall evaluate vaccine effectiveness 9 years post first vaccination. Participants will be evaluated for HPV type specific antibody, genital HPV infection, genital warts and a subset of 30 participants will be evaluated for memory B and T cell responses.

Description:

Genital Human Papilloma Virus (HPV) infections occur rapidly after sexual debut, and immunosuppressed individuals are at greater risk for incident and persistent infection. HPV vaccine contains virus-like participles (VLP), which are highly immunogenic and induce a robust humoral response that has been demonstrated to confer long term protection from HPV infection and associated disease among HIV-uninfected individuals. The magnitude of type-specific vaccine induced neutralizing HPV antibody responses are diminished among HIV-infected compared to uninfected individuals. There is no established minimum level of antibody that predicts protection against HPV infection or associated disease, the impact of lower antibody titers among HIV infected individuals on vaccine efficacy is unknown. The risk of HPV exposure persists throughout a person's sexual life and the duration of protection, especially when the vaccine is given in the early adolescent period is critical to vaccine effectiveness. Long lasting memory is characterized by memory B cells and long-lived plasma cells and a QHPV booster dose has demonstrated an anamnestic response among HIV-infected adolescents. HPV efficacy and effectiveness data for HIV-uninfected individuals has informed the current World Health Organization (WHO) two-dose vaccine schedule. The field lacks data on effectiveness of three dose or two-dose for the HIV-infected adolescents. The current on-going research for single dose schedules gives urgency to the determination of long-term efficacy of three HPV vaccine doses for the HIV-infected adolescent. The Investigators shall recall HIV-infected girls and boys who were previously vaccinated at ages 9-14 years with three doses of the quadrivalent vaccine (QHPV) in 2014 and evaluated for vaccine immunogenicity. Method: The participants will be assessed for genital warts and genital HPV infection. Type specific HPV DNA will be assessed using genital swabs and genital warts assessed through physical examination among sexually active participants at enrollment, month 6 &12. A sub-set of study participants will receive a booster dose of QHPV and evaluated for memory B and T cell responses. The total duration of study follow up will be 12 months

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 135
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 24 Years

Eligibility

Inclusion Criteria:

1. received three doses of the quadrivalent HPV vaccine and enrolled in the quadrivalent HPV vaccine safety and immunogenicity study (MISP 38406)

2. participant consent or parental/guardian consent and participant assent for participants still <18 years of age

3. participants and guardians who consented to be contacted for further evaluation and participation in research and

4. are willing to continue longer-term follow up.

Exclusion Criteria:

1. Did not participate in the quadrivalent HPV vaccine safety and immunogenicity study (MISP 38406)

2. Not willing or able to provide written informed consent/assent to participate in the study

Related Conditions & MeSH terms

• HPV-Related Carcinoma

Intervention

Drug:
• Quadrivalent HPV [Type 6, 11, 16 and 18] L1 Virus-Like Particle Vaccine
No intervention will be administered

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Kenya Medical Research Institute	University of Washington

References & Publications (14)

Banatvala J, Van Damme P, Van Hattum J. Boosters for hepatitis B. European Consensus Group on Hepatitis B Immunity. Lancet. 2000 Jul 22;356(9226):337-8. — View Citation

Einstein MH, Levin MJ, Chatterjee A, Chakhtoura N, Takacs P, Catteau G, Dessy FJ, Moris P, Lin L, Struyf F, Dubin G; HPV-010 Study Group. Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccin — View Citation

Lehtinen M, Lagheden C, Luostarinen T, Eriksson T, Apter D, Harjula K, Kuortti M, Natunen K, Palmroth J, Petäjä T, Pukkala E, Siitari-Mattila M, Struyf F, Nieminen P, Paavonen J, Dubin G, Dillner J. Ten-year follow-up of human papillomavirus vaccine effic — View Citation

Levin MJ, Huang S, Moscicki AB, Song LY, Read JS, Meyer WA, Saah AJ, Richardson K, Weinberg A; IMPAACT P1085 Protocol Team. Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effec — View Citation

MacIntyre CR, Shaw P, Mackie FE, Boros C, Marshall H, Barnes M, Seale H, Kennedy SE, Moa A, Hayen A, Chughtai AA, O'Loughlin EV, Stormon M. Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromise — View Citation

MacIntyre CR, Shaw PJ, Mackie FE, Boros C, Marshall H, Seale H, Kennedy SE, Moa A, Chughtai AA, Trent M, O'Loughlin EV, Stormon M. Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromise — View Citation

Moscicki AB, Karalius B, Tassiopoulos K, Yao TJ, Jacobson DL, Patel K, Purswani M, Seage GR; Pediatric HIV/AIDS Cohort Study. Human Papillomavirus Antibody Levels and Quadrivalent Vaccine Clinical Effectiveness in Perinatally Human Immunodeficiency Virus- — View Citation

Mugo NR, Eckert L, Magaret AS, Cheng A, Mwaniki L, Ngure K, Celum C, Baeten JM, Galloway DA, Wamalwa D, Wald A. Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation — View Citation

Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Høye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Bar — View Citation

Pathak N, Dodds J, Zamora J, Khan K. Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis. BMJ. 2014 Sep 16;349:g5264. doi: 10.1136/bmj.g5264. Review. — View Citation

Pinto LA, Dillner J, Beddows S, Unger ER. Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV vaccine evaluation and development. Vaccine. 2018 Aug 6;36(32 Pt A):4792-4799. doi: 10.1016/j.vaccine.2017.11.089. Epub 2018 Feb 1. — View Citation

Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007 Aug 1;121(3):621-32. — View Citation

Van Keer S, Tjalma WAA, Pattyn J, Biesmans S, Pieters Z, Van Ostade X, Ieven M, Van Damme P, Vorsters A. Human papillomavirus genotype and viral load agreement between paired first-void urine and clinician-collected cervical samples. Eur J Clin Microbiol — View Citation

Weinberg A, Huang S, Moscicki AB, Saah A, Levin MJ; IMPAACT P1085 Protocol Team. Persistence of memory B-cell and T-cell responses to the quadrivalent HPV vaccine in HIV-infected children. AIDS. 2018 Apr 24;32(7):851-860. doi: 10.1097/QAD.0000000000001773 — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in persistent Genital HPV infection	Type specific HPV serotype: -6, -11, -16 and -18 and additional 13 oncogenic HPV serotypes 31,33,35,39,45,51,52,56,58,59,66, 68,73 as per International Agency for Research on Cancer (IARC) monographs.	The changes will be measured at baseline (enrolment), month 6 and 12
Primary	Changes in geometric titers for HPV-specific Antibodies	Vaccine type specific HPV antibody Geometric Mean Titers: HPV- 6, 11, 16 & 18	This outcome will be measured at Month 12
Primary	B-memory cell elicitation in the participants given a booster vaccine	Elicited from Peripheral Blood Mononuclear Cell (PBMC)	This will be measured at 12 months after receiving a booster vaccine

External Links

•   ARC Working Group in 2005, World Health Organization; 2007 [cited 2020 1st July 2020]. HPV monographs. Available from IARC Monographs on the Identification of Carcinogenic Hazards to Humans (who.int)
•   Gardasil product information