Dissecting the influence of HIV infection and treatment with antiretroviral therapy on Human Papillomavirus infection, disease and immunity: Designing new tools for therapeutic intervention.

• Antragsteller: Dr. Christof Geldmacher
• Fachliche Zuordnung: Virologie ; Immunologie ; Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2015 bis 2023
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 270691494

• Erstellungsjahr: 2024

Zusammenfassung der Projektergebnisse

Die Zunahme von Papilloma-Virus (HPV) assoziiertem Gebärmutterkrebs in den HIV+ Frauen lässt vermuten, dass HIV-induzierte Defekte der HPV-spezifischen Immunantwort auch nach Initiierung der Antiretroviralen Therapie (ART) eine wichtige Rolle in der Pathogenese spielen. Die HIV-induzierten Immundefekte führen zu erhöhter Replikation und Persistenz von Hochrisiko (HR) HPV Infektionen, wodurch die Krankheitsprogression zu milder und moderater Zervixdysplasie begünstigt werden. Wir postulieren, dass deutlich erhöhte HR HPV Viruslasten in Gegenwart von Dysplasie die Wahrscheinlichkeit von Integrationsereignissen des HPV Virusgenom in das menschliche Wirtsgenom erhöhen, infolgedessen der Prozess der maligne Zelltransformation beschleunigt wird. Wir glauben, dass eine erhöhte Wahrscheinlichkeit von HPV DNA Integrationsereignissen das Zellgenom, die deutlich beschleunigte Kanzerogenese in HIV+ Frauen erklären können. Wir postulieren, daß ein therapeutischer Impfstoff die HPV-spezifische adaptive Immunität wiederbeleben kann, um persistente HPV Infektionen in HIV+ Frauen auf ART zu therapieren und so die Kanzerogenese frühzeitig zu unterbinden. Folglich soll die vorgeschlagene Studie die komplizierten Wechselwirkungen zwischen HIV, dem Immunsystem und HPV verursachter Karzinogenese in der Ära von ART analysieren.

Projektbezogene Publikationen (Auswahl)

• 30th National Institute of Medical Research (NIMR)- Annual Scientific Conference in Arusha 2016, "The 2H study in Mbeya from April 2013 to June 2016". This presentation was the overall winner 2016 of the Mount Kilimanjaro Scientific Award.
  Ruby Mcharo
  
• Conference on Retroviruses and Opportunistic Infections (CROI) in Boston 2016, " High Prevalence of HR-HPV Infection in HIV-Infected Women From Tanzania".
  Arne Kroidl
  
• "Distribution of Human papilloma virus (HPV) among women enrolled in cervical cancer study in Mbeya- Tanzania". This presentation was awarded 1st Prize for best poster presentation (HIV and Global Health track).
  Jonathan Mnkai
  
• 7th Symposium Infectious Diseases in Africa (IDA) in Cape Town, 2017, "Dissecting the influence of HIV infection and treatment with ART on HPV infection, disease and immunity" This presentation was awarded with 1st price for best oral presentation.
  Wilbert Mbuya
  
• 7th Symposium Infectious Diseases in Africa (IDA) in Cape Town, 2017, "Phenotyping mucosal T-Cells in HIV- and HIV+ women with/without pre-cancerous cervical lesions/invasive cancer in Mbeya - Tanzania".
  Jacklina Mhidze
  
• Depletion and activation of mucosal CD4 T cells in HIV infected women with HPV-associated lesions of the cervix uteri. PLOS ONE, 15(10), e0240154.
  Mbuya, Wilbert; Mcharo, Ruby; Mhizde, Jacklina; Mnkai, Jonathan; Mahenge, Anifrid; Mwakatima, Maria; Mwalongo, Wolfram; Chiwerengo, Nhamo; Hölscher, Michael; Lennemann, Tessa; Saathoff, Elmar; Rwegoshora, France; Torres, Liset; Kroidl, Arne; Geldmacher, Christof; Held, Kathrin & Chachage, Mkunde
  
• Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV. Frontiers in Immunology, 12.
  Mbuya, Wilbert; Held, Kathrin; Mcharo, Ruby D.; Haule, Antelmo; Mhizde, Jacklina; Mnkai, Jonathan; Mahenge, Anifrid; Mwakatima, Maria; Sembo, Margareth; Mwalongo, Wolfram; Agrea, Peter; Hoelscher, Michael; Maboko, Leonard; Saathoff, Elmar; Geisenberger, Otto; Rwegoshora, France; Torres, Liset; Koup, Richard A.; Kroidl, Arne ... & Geldmacher, Christof
  
• HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer in East Africa. Frontiers in Oncology, 11.
  Mcharo, Ruby; Lennemann, Tessa; France, John; Torres, Liseth; Garí, Mercè; Mbuya, Wilbert; Mwalongo, Wolfram; Mahenge, Anifrid; Bauer, Asli; Mnkai, Jonathan; Glasmeyer, Laura; Judick, Mona; Paul, Matilda; Schroeder, Nicolas; Msomba, Bareke; Sembo, Magreth; Chiwerengo, Nhamo; Hoelscher, Michael; Geisenberger, Otto ... & Geldmacher, Christof
  
• Eurogin in Düsseldorf, 2022, “HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer South West Tanzania”
  Christof Geldmacher
  
• European Congress on Gynecological Oncology in Berlin, 2022, “MULTIPLEXED BIOMARKER DETECTION USING THE QUANTIGENE ASSAY IN WOMEN LIVING WITH HIV FOR CERVICAL DYSPLASIA DETECTION”
  Anna Sophie Skof
  
• High-risk human papillomavirus genotype distribution among women living with and at risk for HIV in Africa. AIDS, 37(4), 625-635.
  Chachage, Mkunde; Parikh, Ajay P.; Mahenge, Anifrid; Bahemana, Emmanuel; Mnkai, Jonathan; Mbuya, Wilbert; Mcharo, Ruby; Maganga, Lucas; Mwamwaja, Jaqueline; Gervas, Reginald; Kibuuka, Hannah; Maswai, Jonah; Singoei, Valentine; Iroezindu, Michael; Fasina, Abiola; Esber, Allahna; Dear, Nicole; Imbach, Michelle; Crowell, Trevor A. ... & Geldmacher, Christof
  
• Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting. BMC Cancer, 22(1).
  Glasmeyer, Laura; Mcharo, Ruby Doryn; Torres, Liset; Lennemann, Tessa; Danstan, Elizabeth; Mwinuka, Nice; Judick, Mona; Mueller, William; Mbuya, Wilbert; Hölscher, Michael; Lellé, Ralph; Geldmacher, Christof; Kroidl, Arne & France, John Rwegoshora
  
• 35th IPVC conference in Washington DC, 2023, ”HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer South West Tanzania” This presentation was awarded with a IPVC 2023 Travel Scholarship
  Wilbert Mbuya
  
• Therapeutic Efficacy of a VSV-GP-based Human Papilloma Virus Vaccine in a Murine Cancer Model. Journal of Molecular Biology, 435(13), 168096.
  Riepler, Lydia; Frommelt, Laura-Sophie; Wilmschen-Tober, Sarah; Mbuya, Wilbert; Held, Kathrin; Volland, André; von Laer, Dorothee; Geldmacher, Christof & Kimpel, Janine
  
• 36th IPVC conference in Edinburgh, 2024, “DISSECTING THE IMPACT OF HIV ON HPV-SPECIFIC IMMUNITY, VIRAL PERSISTENCE AND MOLECULAR SIGNATURES OF CERVICAL DYSPLASIA”
  Wilbert Mbuya
  
• NIMR conference in 2024, “Quantification of cervical cancer causing HPV16 E6 and E7 oncogene-transcripts in women living with and without HIV in Mbeya, Tanzania.”
  Wilbert Mbuya