Role of the intestinal microbiome in the immunopathogenesis of HPV disease and response to a nine-valent anti-HPV vaccine in HIV-infected positive males
Italy (SISM) - University of Milan, Milan
Infectious Diseases
Department of Health Sciences-Clinic of Infectious Diseases
Giulia Marchetti, M.D., Ph.D., Camilla Tincati, M.D., Ph.D., Debora Mondatore M.D., Stefania Cannizzo, Ph.D.
Giulia Marchetti, M.D., Ph.D., Camilla Tincati, M.D., Ph.D., Debora Mondatore M.D., Stefania Cannizzo, Ph.D.
English, Italian
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No Yes No No No No No No Yes
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
HIV-infected are at risk of HPV clinical progression. HIV-HPV is of particular interest in HIV-infected Men who have Sex with Men (MSM), given a reported 130-fold higher risk of HPV-related anal cancer compared to HIV-uninfected. Sexual behaviour plays a role in the acquisition of high-risk and multiple HPV genotypes, and impairment of HPV- specific immunity hinders the host’s ability to clear infection, which persists as a causative agent for the development of genital dysplasia and cancer. Understanding the ways by which defects in HPV-specific immunity arise in the setting of HIV disease is thus vital to determine efficient preventive measures and alternative therapeutic interventions. The GI tract has a pivotal role in the pathogenesis of HIV-related immune-deficiency; HIV dysbiosis has also been described, especially in MSM, which may drive HIV clinical progression as well as HPV-related disease progression. Whether the composition of the intestinal dysbiosis impacts on HPV-specific immunity, however, is currently unknown. In order to combat HIV-HPV co-infection, guidelines recommend 9-valent anti-HPV vaccination in co-infected individuals. Recent studies have shown that the host’s microbiome may influence the response to vaccination; this finding together with the reported data on HIV dysbiosis leads us to hypothesize that the microbiome of HIV-infected MSM may modulate the response to an anti-HPV vaccine.
What is the aim of the project?
The first aim of the project will evaluate the role of intestinal microbiome in the immunopathogenesis of HPV-infection in a cohort of HIV-positive MSM on suppressive combination antiretroviral therapy (cART). The second aim of the project evaluate the role of intestinal microbiome in modulating the response to 9-valent anti-HPV vaccination in a cohort of HIV-infected male individuals on cART
What techniques and methods are used?
The design of our research proposal is cross-sectional and longitudinal. We will enrol 100 HIV-infected subjects on suppressive cART who will undergo 9-valent anti-HPV vaccination. Prior to vaccination (T0) and 1 month (T_finale) after the end of the vaccination schedule, the following procedures will be carried out: i) surgical evaluation with anal cytology (PAP smear) and HPV genotyping ii) collection of anal brushing for microbiome analysis (16S rDNA quantification and metagenomic sequencing Illumina technology) iii) collection of peripheral blood for peripheral blood mononuclear cells (PBMC) and plasma separation which will be used for the study, respectively of HPV-specific responses (flow cytometry) and HPV antibody titration (commercial ELISA) Anal microbiome composition will be correlated to specific T-cells response to HPV-antigens and to the grade of anal dysplasia before and after immunization with 9-valent vaccine.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
At the end of the internship, the student will have gained insights into the clinical management of HIV-HPV co-infection and anal dysplasia, particularly as a result of the aforementioned co-infection. From a research perspective, the student will have learned how to separate peripheral blood mononuclear cells (PBMCs) and plasma from whole blood samples and perform staining with monoclonal antibodies for flow cytometry experiments.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare an abstract
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- 1. Tincati C; Rainone V; Comi L; et al. Cell-Mediated Immunity in HIV-Infected Males With Human Papillomavirus-Related Anal Dysplastic Lesions. Clin Infect Dis 2016; 63(10): 1396-8.
- 2. Serrano-Villar S; Vásquez-Domínguez E; Pérez-Molina JA; et al. HIV; HPV; and microbiota: partners in crime? AIDS 2017; 31(4): 591-4.
- 3. Rainone V; Giacomet V; Penagini F; et al. Human papilloma virus vaccination induces strong human papilloma virus specific cell-mediated immune responses in HIV-infected adolescents and young adults. AIDS 2015; 29(6): 739-43.