Catia T Perciani1, Bashir Farah2, Rupert Kaul1,3,4, Mario A Ostrowski1,3,5, Salaheddin M Mahmud6, Omu Anzala2,7, Walter Jaoko2,7, Kelly S MacDonald1,8,9. 1. Department of Immunology, University of Toronto, Toronto, Ontario, Canada. 2. Kenyan AIDS Vaccine Initiative-Institute of Clinical Research (KAVI-ICR), University of Nairobi, Nairobi, Kenya. 3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 4. University Health Network, Toronto, Ontario, Canada. 5. Keenan Research Center, St. Michael's Hospital, Toronto, Ontario, Canada. 6. Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 7. Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya. 8. Section of Infectious Diseases, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 9. Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Abstract
BACKGROUND:Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS:Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02514018. FUNDING: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
RCT Entities:
BACKGROUND:Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02514018. FUNDING: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
Entities:
Keywords:
AIDS vaccine; AIDS/HIV; Cytokines; T cells; Vaccines
Authors: Philippe Van de Perre; Michel Segondy; Vincent Foulongne; Abdoulaye Ouedraogo; Issouf Konate; Jean-Marie Huraux; Philippe Mayaud; Nicolas Nagot Journal: Lancet Infect Dis Date: 2008-08 Impact factor: 25.071
Authors: Danilo R Casimiro; Kara Cox; Aimin Tang; Kara J Sykes; Meizhen Feng; Fubao Wang; Andrew Bett; William A Schleif; Xiaoping Liang; Jessica Flynn; Timothy W Tobery; Keith Wilson; Adam Finnefrock; Lingyi Huang; Salvatore Vitelli; Jing Lin; Deepa Patel; Mary-Ellen Davies; Gwendolyn J Heidecker; Daniel C Freed; Sheri Dubey; David H O'Connor; David I Watkins; Zhi-Qiang Zhang; John W Shiver Journal: J Virol Date: 2009-12-30 Impact factor: 5.103
Authors: V R Joag; L R McKinnon; J Liu; S T Kidane; M H Yudin; B Nyanga; S Kimwaki; K E Besel; J O Obila; S Huibner; J O Oyugi; J Arthos; O Anzala; J Kimani; M A Ostrowski; R Kaul Journal: Mucosal Immunol Date: 2015-04-15 Impact factor: 7.313
Authors: John W Shiver; Tong-Ming Fu; Ling Chen; Danilo R Casimiro; Mary-Ellen Davies; Robert K Evans; Zhi-Qiang Zhang; Adam J Simon; Wendy L Trigona; Sheri A Dubey; Lingyi Huang; Virginia A Harris; Romnie S Long; Xiaoping Liang; Larry Handt; William A Schleif; Lan Zhu; Daniel C Freed; Natasha V Persaud; Liming Guan; Kara S Punt; Aimin Tang; Minchun Chen; Keith A Wilson; Kelly B Collins; Gwendolyn J Heidecker; V Rose Fernandez; Helen C Perry; Joseph G Joyce; Karen M Grimm; James C Cook; Paul M Keller; Denise S Kresock; Henryk Mach; Robert D Troutman; Lynne A Isopi; Donna M Williams; Zheng Xu; Kathryn E Bohannon; David B Volkin; David C Montefiori; Ayako Miura; Georgia R Krivulka; Michelle A Lifton; Marcelo J Kuroda; Jörn E Schmitz; Norman L Letvin; Michael J Caulfield; Andrew J Bett; Rima Youil; David C Kaslow; Emilio A Emini Journal: Nature Date: 2002-01-17 Impact factor: 49.962
Authors: Xiaoping Liang; Danilo R Casimiro; William A Schleif; Fubao Wang; Mary-Ellen Davies; Zhi-Qiang Zhang; Tong-Ming Fu; Adam C Finnefrock; Larry Handt; Michael P Citron; Gwendolyn Heidecker; Aimin Tang; Minchun Chen; Keith A Wilson; Lori Gabryelski; Michael McElhaugh; Anthony Carella; Cheryl Moyer; Lingyi Huang; Salvatore Vitelli; Deepa Patel; Jing Lin; Emilio A Emini; John W Shiver Journal: J Virol Date: 2005-10 Impact factor: 5.103
Authors: Scott M Hammer; Magdalena E Sobieszczyk; Holly Janes; Shelly T Karuna; Mark J Mulligan; Doug Grove; Beryl A Koblin; Susan P Buchbinder; Michael C Keefer; Georgia D Tomaras; Nicole Frahm; John Hural; Chuka Anude; Barney S Graham; Mary E Enama; Elizabeth Adams; Edwin DeJesus; Richard M Novak; Ian Frank; Carter Bentley; Shelly Ramirez; Rong Fu; Richard A Koup; John R Mascola; Gary J Nabel; David C Montefiori; James Kublin; M Juliana McElrath; Lawrence Corey; Peter B Gilbert Journal: N Engl J Med Date: 2013-10-07 Impact factor: 91.245
Authors: M J Levin; M N Oxman; J H Zhang; G R Johnson; H Stanley; A R Hayward; M J Caulfield; M R Irwin; J G Smith; J Clair; I S F Chan; H Williams; R Harbecke; R Marchese; S E Straus; A Gershon; A Weinberg Journal: J Infect Dis Date: 2008-03-15 Impact factor: 5.226
Authors: Siddappa N Byrareddy; Brianne Kallam; James Arthos; Claudia Cicala; Fatima Nawaz; Joseph Hiatt; Ellen N Kersh; Janet M McNicholl; Debra Hanson; Keith A Reimann; Markus Brameier; Lutz Walter; Kenneth Rogers; Ann E Mayne; Paul Dunbar; Tara Villinger; Dawn Little; Tristram G Parslow; Philip J Santangelo; Francois Villinger; Anthony S Fauci; Aftab A Ansari Journal: Nat Med Date: 2014-11-24 Impact factor: 53.440