Induction of HIV-1-specific Mucosal Immune Responses Following Intramuscular Recombinant Adenovirus Serotype 26 HIV-1 Vaccination of Humans

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2014 Aug 29

PMID 25165165

Citations 45

Authors

Lindsey R Baden

Jinyan Liu

Hualin Li

Jennifer A Johnson

Stephen R Walsh

Jane A Kleinjan

Brian A Engelson

Lauren Peter

Peter Abbink

Danny A Milner Jr

Kevin L Golden

Kyle L Viani

Matthew D Stachler

Benjamin J Chen

Maria G Pau

Mo Weijtens

Brittany R Carey

Caroline A Miller

Edith M Swann

Mark Wolff

Hayley Loblein

Michael S Seaman

Raphael Dolin

Dan H Barouch

Affiliations

Soon will be listed here.

Abstract

Background: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.

Methods: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed.

Results: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry.

Conclusions: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.

Clinical Trials Registration: NCT01103687.

Citing Articles

Advances of Recombinant Adenoviral Vectors in Preclinical and Clinical Applications.

Scarsella L, Ehrke-Schulz E, Paulussen M, Thal S, Ehrhardt A, Aydin M Viruses. 2024; 16(3).

PMID: 38543743 PMC: 10974029. DOI: 10.3390/v16030377.

Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.

Trivedi P, Byrne B, Corti M Viruses. 2023; 15(12).

PMID: 38140619 PMC: 10747483. DOI: 10.3390/v15122378.

Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination.

Aid M, Stephenson K, Collier A, Nkolola J, Michael J, McKenzie S Nat Commun. 2023; 14(1):6703.

PMID: 37872311 PMC: 10593859. DOI: 10.1038/s41467-023-42559-x.

Sequential use of Ad26-based vaccine regimens in NHP to induce immunity against different disease targets.

Khan S, Salisch N, Izquierdo Gil A, Boedhoe S, Feddes-de Boer K, Serroyen J NPJ Vaccines. 2022; 7(1):146.

PMID: 36379957 PMC: 9664441. DOI: 10.1038/s41541-022-00567-w.

The use of adenoviral vectors in gene therapy and vaccine approaches.

Araujo N, Rubio I, Toneto N, Morale M, Tamura R Genet Mol Biol. 2022; 45(3 Suppl 1):e20220079.

PMID: 36206378 PMC: 9543183. DOI: 10.1590/1678-4685-GMB-2022-0079.

References

McElrath M, De Rosa S, Moodie Z, Dubey S, Kierstead L, Janes H . HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet. 2008; 372(9653):1894-1905. PMC: 2774110. DOI: 10.1016/S0140-6736(08)61592-5. View

Barouch D, Liu J, Li H, Maxfield L, Abbink P, Lynch D . Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature. 2012; 482(7383):89-93. PMC: 3271177. DOI: 10.1038/nature10766. View

Frahm N, deCamp A, Friedrich D, Carter D, Defawe O, Kublin J . Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest. 2011; 122(1):359-67. PMC: 3248307. DOI: 10.1172/JCI60202. View

Li H, Rhee E, Masek-Hammerman K, Teigler J, Abbink P, Barouch D . Adenovirus serotype 26 utilizes CD46 as a primary cellular receptor and only transiently activates T lymphocytes following vaccination of rhesus monkeys. J Virol. 2012; 86(19):10862-5. PMC: 3457266. DOI: 10.1128/JVI.00928-12. View

Penaloza-MacMaster P, Provine N, Ra J, Borducchi E, McNally A, Simmons N . Alternative serotype adenovirus vaccine vectors elicit memory T cells with enhanced anamnestic capacity compared to Ad5 vectors. J Virol. 2012; 87(3):1373-84. PMC: 3554181. DOI: 10.1128/JVI.02058-12. View

Li H, Liu J, Carville A, Mansfield K, Lynch D, Barouch D . Durable mucosal simian immunodeficiency virus-specific effector memory T lymphocyte responses elicited by recombinant adenovirus vectors in rhesus monkeys. J Virol. 2011; 85(21):11007-15. PMC: 3194971. DOI: 10.1128/JVI.05346-11. View

Fauci A, Marovich M, Dieffenbach C, Hunter E, Buchbinder S . Immunology. Immune activation with HIV vaccines. Science. 2014; 344(6179):49-51. PMC: 4414116. DOI: 10.1126/science.1250672. View

Perreau M, Welles H, Harari A, Hall O, Martin R, Maillard M . DNA/NYVAC vaccine regimen induces HIV-specific CD4 and CD8 T-cell responses in intestinal mucosa. J Virol. 2011; 85(19):9854-62. PMC: 3196391. DOI: 10.1128/JVI.00788-11. View

Duerr A, Huang Y, Buchbinder S, Coombs R, Sanchez J, Del Rio C . 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). J Infect Dis. 2012; 206(2):258-66. PMC: 3490694. DOI: 10.1093/infdis/jis342. View

10.

Sprangers M, Lakhai W, Koudstaal W, Verhoeven M, Koel B, Vogels R . Quantifying adenovirus-neutralizing antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine and gene therapy vectors. J Clin Microbiol. 2003; 41(11):5046-52. PMC: 262545. DOI: 10.1128/JCM.41.11.5046-5052.2003. View

11.

Hutnick N, Carnathan D, Dubey S, Makedonas G, Cox K, Kierstead L . Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat Med. 2009; 15(8):876-8. PMC: 2723179. DOI: 10.1038/nm.1989. View

12.

Liu J, Ewald B, Lynch D, Denholtz M, Abbink P, Lemckert A . Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys. J Virol. 2008; 82(10):4844-52. PMC: 2346755. DOI: 10.1128/JVI.02616-07. View

13.

Liu J, OBrien K, Lynch D, Simmons N, La Porte A, Riggs A . Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature. 2008; 457(7225):87-91. PMC: 2614452. DOI: 10.1038/nature07469. View

14.

Mast T, Kierstead L, Gupta S, Nikas A, Kallas E, Novitsky V . International epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and type-36 neutralizing antibodies: correlates of high Ad5 titers and implications for potential HIV vaccine trials. Vaccine. 2009; 28(4):950-7. DOI: 10.1016/j.vaccine.2009.10.145. View

15.

Tan W, Jin H, West E, Penaloza-MacMaster P, Wieland A, Zilliox M . Comparative analysis of simian immunodeficiency virus gag-specific effector and memory CD8+ T cells induced by different adenovirus vectors. J Virol. 2012; 87(3):1359-72. PMC: 3554140. DOI: 10.1128/JVI.02055-12. View

16.

Hammer S, Sobieszczyk M, Janes H, Karuna S, Mulligan M, Grove D . Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013; 369(22):2083-92. PMC: 4030634. DOI: 10.1056/NEJMoa1310566. View

17.

Barouch D, Kik S, Weverling G, Dilan R, King S, Maxfield L . International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine. 2011; 29(32):5203-9. PMC: 3138857. DOI: 10.1016/j.vaccine.2011.05.025. View

18.

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R . Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009; 361(23):2209-20. DOI: 10.1056/NEJMoa0908492. View

19.

Flynn N, Forthal D, Harro C, Judson F, Mayer K, Para M . Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005; 191(5):654-65. DOI: 10.1086/428404. View

20.

Letvin N, Rao S, Montefiori D, Seaman M, Sun Y, Lim S . Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys. Sci Transl Med. 2011; 3(81):81ra36. PMC: 3718279. DOI: 10.1126/scitranslmed.3002351. View