A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults

PLoS ONE

Volumn 7, Issue 8, 2012, Pages

  Keefer, Michael C ^a   Gilmour, Jill ^b   Hayes, Peter ^b   Gill, Dilbinder ^b   Kopycinski, Jakub ^b   Cheeseman, Hannah ^b   Cashin Cox, Michelle ^b   Naarding, Marloes ^b   Clark, Lorna ^b   Fernandez, Natalia ^b   Bunce, Catherine A ^a   Hay, Christine M ^a   Welsh, Sabrina ^c   Komaroff, Wendy ^c   Hachaambwa, Lottie ^a   Tarragona Fiol, Tony ^b   Sayeed, Eddy ^c   Zachariah, Devika ^c   Ackland, James ^d   Loughran, Kelley ^e   Barin, Burc ^e   Cormier, Emmanuel ^b   Cox, Josephine H ^b   Fast, Patricia ^c   Excler, Jean Louis ^c   more..

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c INTERNATIONAL AIDS VACCINE INITIATIVE   (United States)

^d Global BioSolutions   (Australia)

^e EMMES CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; GAG PROTEIN; GAMMA INTERFERON; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; INTEGRASE; NEF PROTEIN; PLACEBO; RNA DIRECTED DNA POLYMERASE; VIRUS ENVELOPE PROTEIN;

ADULT; ANTIBODY TITER; ARTHRALGIA; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CHILL; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FLU LIKE SYNDROME; GENETIC IMMUNIZATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNOGENICITY; INJECTION SITE ANESTHESIA; INJECTION SITE BLEEDING; INJECTION SITE ERYTHEMA; INJECTION SITE INDURATION; INJECTION SITE PAIN; INJECTION SITE REACTION; INJECTION SITE SWELLING; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALAISE; MALE; MYALGIA; NOSE CONGESTION; PHARYNGITIS; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SORE THROAT; SYSTEMIC DISEASE; UNSPECIFIED SIDE EFFECT; UPPER RESPIRATORY TRACT INFECTION; VIRUS PARTICLE; VIRUS RECOMBINANT;

ADENOVIRUSES, HUMAN; ADOLESCENT; ADULT; AIDS VACCINES; ANTIBODIES, VIRAL; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; DOUBLE-BLIND METHOD; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; MALE; MIDDLE AGED; RETROVIRIDAE PROTEINS; VACCINATION;

ADENOVIRIDAE; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84864542615     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0041936     Document Type: Article

References (64)

1. UNAIDS (2011) Global HIV/AIDS Response. Epidemic update and health sector progress towards Universal Access. Progress Report 2011.
2. Fauci AS, Johnston MI, Dieffenbach CW, Burton DR, Hammer SM, et al. (2008) HIV vaccine research: the way forward. Science 321: 530-532.
3. Kim JH, Rerks-Ngarm S, Excler JL, Michael NL, (2010) HIV vaccines: lessons learned and the way forward. Curr Opin HIV AIDS 5: 428-434.
4. Haynes BF, Shattock RJ (2008) Critical issues in mucosal immunity for HIV-1 vaccine development. J Allergy Clin Immunol 122: 3-9; quiz 10-11.
5. Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, et al. (2005) Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 191: 654-665.
6. Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, et al. (2006) Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 194: 1661-1671.
7. Koff WC, (2010) Accelerating HIV vaccine development. Nature 464: 161-162.
8. Nabel GJ, Kwong PD, Mascola JR, (2011) Progress in the rational design of an AIDS vaccine. Philos Trans R Soc Lond B Biol Sci 366: 2759-2765.
9. Bonsignori M, Hwang KK, Chen X, Tsao CY, Morris L, et al. (2011) Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol 85: 9998-10009.
10. McLellan JS, Pancera M, Carrico C, Gorman J, Julien JP, et al. (2011) Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480: 336-343.
11. Scheid JF, Mouquet H, Ueberheide B, Diskin R, Klein F, et al. (2011) Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333: 1633-1637.
12. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, et al. (2011) Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477: 466-470.
13. Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326: 285-289.
14. Wu X, Yang ZY, Li Y, Hogerkorp CM, (2010) Schief WR, et al (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329: 856-861.
15. Wu X, Zhou T, Zhu J, Zhang B, Georgiev I, et al. (2011) Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science 333: 1593-1602.
16. Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, et al. (2010) Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329: 811-817.
17. Korber BT, Letvin NL, Haynes BF, (2009) T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces. J Virol 83: 8300-8314.
18. Walker BD, Burton DR, (2008) Toward an AIDS vaccine. Science 320: 760-764.
19. Engram JC, Dunham RM, Makedonas G, Vanderford TH, Sumpter B, et al. (2009) Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression. J Immunol 183: 706-717.
20. Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, et al. (2011) Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473: 523-527.
21. Mattapallil JJ, Douek DC, Buckler-White A, Montefiori D, Letvin NL, et al. (2006) Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. J Exp Med: 1533-1541.
22. Vaccari M, Mattapallil J, Song K, Tsai WP, Hryniewicz A, et al. (2008) Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency. J Virol 82: 9629-9638.
23. Watkins D, Burton DR, Kallas EG, Moore JP, Koff WC, (2008) Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans. Nat Med 14: 617-621.
24. Wilson NA, Reed J, Napoe GS, Piaskowski S, Szymanski A, et al. (2006) Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239. J Virol 80: 5875-5885.
25. Gupta SB, Jacobson LP, Margolick JB, Rinaldo CR, Phair JP, et al. (2007) Estimating the benefit of an HIV-1 vaccine that reduces viral load set point. J Infect Dis 195: 546-550.
26. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, et al. (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372: 1881-1893.
27. McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, et al. (2008) HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372: 1894-1905.
28. Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, et al. (2011) Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis. 11: 507-515.
29. D'Souza MP, Frahm N, (2010) Adenovirus 5 serotype vector-specific immunity and HIV-1 infection: a tale of T cells and antibodies. AIDS 24: 803-809.
30. Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, et al. (2012) Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step study). Journal of Infectious Diseases. doi: 10.1093/infdis/jis342.
31. Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, et al. (2008) Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis 46: 1769-1781.
32. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, et al. (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361: 2209-2220.
33. Kostense S, Koudstaal W, Sprangers M, Weverling GJ, Penders G, et al. (2004) Adenovirus types 5 and 35 seroprevalence in AIDS risk groups supports type 35 as a vaccine vector. AIDS 18: 1213-1216.
34. Vogels R, Zuijdgeest D, van Rijnsoever R, Hartkoorn E, Damen I, et al. (2003) Replication-Deficient Human Adenovirus Type 35 Vectors for Gene Transfer and Vaccination: Efficient Human Cell Infection and Bypass of Preexisting Adenovirus Immunity. J Virol 77: 8263-8271.
35. Barouch DH, Kik SV, Weverling GJ, Dilan R, King SL, et al. (2011) International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine 29: 5203-5209.
36. Ni S, Bernt K, Gaggar A, Li ZY, Kiem HP, et al. (2005) Evaluation of biodistribution and safety of adenovirus vectors containing group B fibers after intravenous injection into baboons. Hum Gene Ther 16: 664-677.
37. Abel B, Tameris M, Mansoor N, Gelderbloem S, Hughes J, et al. (2010) The Novel Tuberculosis Vaccine, AERAS-402, Induces Robust and Polyfunctional CD4+ and CD8+ T Cells in Adults. American Journal of Respiratory and Critical Care Medicine 181: 1407-1417.
38. Stiles T, Grant V, Mawbey T, (2010) Good Clinical Laboratory Practice (GCLP). A quality sytem for laboratories that undertake the analysis of samples from clinical trials; Assurance. BARQA ISBN 978-1-904610-00-7: pp. 1-17.
39. Cox JH, Ferrari G, Kalams S, Lopaczynski W, Oden N, et al. (2005) Results of an ELISPOT Proficiency Panel Conducted in 11 Laboratories Participating in International Human Immunodeficiency Virus Type 1 Vaccine trials. AIDS res Hum Retroviruses 21: 68-81.
40. Jaimes MC, Maecker HT, Yan M, Maino VC, Hanley MB, et al. (2011) Quality assurance of intracellular cytokine staining assays: analysis of multiple rounds of proficiency testing. J Immunol Methods 363: 143-157.
41. Sarzotti-Kelsoe M, Cox J, Cleland N, Denny T, Hural J, et al. (2009) Evaluation and Recommendations on Good Clinical Laboratory Practice Guidelines for Phase I-III Clinical Trials. PLoS Med 6: e1000067.
42. Sprangers MC, Lakhai W, Koudstaal W, Verhoeven M, Koel BF, et al. (2003) Quantifying Adenovirus-Neutralizing Antibodies by Luciferase Transgene Detection: Addressing Preexisting Immunity to Vaccine and Gene Therapy Vectors. J Clin Microbiol 41: 5046-5052.
43. Richman DD, Wrin T, Little SJ, Petropoulos CJ, (2003) Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci USA 100: 4144-4149.
44. Boaz MJ, Hayes P, Tarragona T, Seamons L, Cooper A, et al. (2009) Concordant Proficiency in Measurement of T-Cell Immunity in Human Immunodeficiency Virus Vaccine Clinical Trials by Peripheral Blood Mononuclear Cell and Enzyme-Linked Immunospot Assays in Laboratories from Three Continents. Clin Vaccine Immunol 16: 147-155.
45. Jaoko W, Karita E, Kayitenkore K, Omosa-Manyonyi G, Allen S, et al. (2010) Safety and Immunogenicity Study of Multiclade HIV-1 Adenoviral Vector Vaccine Alone or as Boost following a Multiclade HIV-1 DNA Vaccine in Africa. PLoS ONE 5: e12873.
46. Roederer M, Nozzi JL, Nason MC, (2011) SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 79: 167-174.
47. Perfetto S, Ambrozak D, Nguyen R, Chattopadhyay PK, Roederer M, (2006) Quality Assurance for Polychromatic Flow Cytometry Nature Protocols. 1: 1522-1530.
48. Frahm N, DeCamp AC, Friedrich DP, Carter DK, Defawe OD, et al. (2012) Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest 122: 359-367.
49. Barouch DH, Liu J, Li H, Maxfield LF, Abbink P, et al. (2012) Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482: 89-93.
50. Böckl K, Wild J, Bredl S, Kindsmüller K, Köstler J, et al. (2012) Altering an Artificial Gagpolnef Polyprotein and Mode of ENV Co-Administration Affects the Immunogenicity of a Clade C HIV DNA Vaccine. PLoS ONE 7: e34723.
51. Hel Z, Tsai WP, Tryniszewska E, Nacsa J, Markham PD, et al. (2006) Improved vaccine protection from simian AIDS by the addition of nonstructural simian immunodeficiency virus genes. J Immunol 176: 85-96.
52. Toapanta FR, Craigo JK, Montelaro RC, Ross TM, (2007) Reduction of anti-HIV-1 Gag immune responses during co-immunization: immune interference by the HIV-1 envelope. Curr HIV Res 5: 199-209.
53. Harari A, Bart PA, Stohr W, Tapia G, Garcia M, et al. (2008) An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 205: 63-77.
54. Vasan S, Schlesinger SJ, Huang Y, Hurley A, Lombardo A, et al. (2010) Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-Based Clade C/B' HIV-1 Candidate Vaccine. PLoS ONE 5: e8617.
55. Fioretti D, Iurescia S, Fazio VM, Rinaldi M, (2010) DNA vaccines: developing new strategies against cancer. J Biomed Biotechnol 2010: 174378.
56. Girard MP, Osmanov S, Assossou OM, Kieny MP, (2011) Human immunodeficiency virus (HIV) immunopathogenesis and vaccine development: a review. Vaccine 29: 6191-6218.
57. Hutnick NA, Myles DJ, Bian CB, Muthumani K, Weiner DB, (2011) Selected approaches for increasing HIV DNA vaccine immunogenicity in vivo. Curr Opin Virol 1: 233-240.
58. Reyes-Sandoval A, Rollier CS, Milicic A, Bauza K, Cottingham MG, et al. (2012) Mixed Vector Immunization With Recombinant Adenovirus and MVA Can Improve Vaccine Efficacy While Decreasing Antivector Immunity. Mol Ther. doi: 10.1038/mt.2012.25.
59. Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, et al. (2012) Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors. PLoS ONE 7: e31208.
60. Li F, Finnefrock AC, Dubey SA, Korber BT, Szinger J, et al. (2011) Mapping HIV-1 Vaccine Induced T-Cell Responses: Bias towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study. PLoS ONE 6: e20479.
61. Rolland M, Tovanabutra S, deCamp AC, Frahm N, Gilbert PB, et al. (2011) Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat Med 17: 366-371.
62. Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, et al. (2010) Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med 16: 319-323.
63. Letourneau S, Im EJ, Mashishi T, Brereton C, Bridgeman A, et al. (2007) Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine. PLoS ONE 2: e984.
64. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, et al. (2012) Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. New England Journal of Medicine 366: 1275-1286.