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Review

Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials

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Pages 379-393 | Published online: 09 Jan 2014

References

  • Kim PS, Ahmed R. Features of responding T cells in cancer and chronic infection. Curr. Opin. Immunol. 22(2), 223–230 (2010).
  • Haynes BF, Gilbert PB, McElrath MJ et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366(14), 1275–1286 (2012).
  • McDermott AB, Koup RA. CD8(+) T cells in preventing HIV infection and disease. AIDS 26(10), 1281–1292 (2012).
  • Mudd PA, Martins MA, Ericsen AJ et al. Vaccine-induced CD8+ T cells control AIDS virus replication. Nature 491(7422), 129–133 (2012).
  • Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S et al.; MOPH-TAVEG Investigators. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361(23), 2209–2220 (2009).
  • Moss B. Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proc. Natl Acad. Sci. USA 93(21), 11341–11348 (1996).
  • Paoletti E, Taylor J, Meignier B, Meric C, Tartaglia J. Highly attenuated poxvirus vectors: NYVAC, ALVAC and TROVAC. Dev. Biol. Stand. 84, 159–163 (1995).
  • Parrino J, Graham BS. Smallpox vaccines: Past, present, and future. J. Allergy Clin. Immunol. 118(6), 1320–1326 (2006).
  • Ockenhouse CF, Sun PF, Lanar DE et al. Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria. J. Infect. Dis. 177(6), 1664–1673 (1998).
  • McConkey SJ, Reece WH, Moorthy VS et al. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat. Med. 9(6), 729–735 (2003).
  • Harari A, Bart PA, Stöhr W et al. An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J. Exp. Med. 205(1), 63–77 (2008).
  • Berthoud TK, Hamill M, Lillie PJ et al. Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clin. Infect. Dis. 52(1), 1–7 (2011).
  • Lillie PJ, Berthoud TK, Powell TJ et al. Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. Clin. Infect. Dis. 55(1), 19–25 (2012).
  • McShane H, Pathan AA, Sander CR et al. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat. Med. 10(11), 1240–1244 (2004).
  • Scriba TJ, Tameris M, Mansoor N et al. Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells. Eur. J. Immunol. 40(1), 279–290 (2010).
  • Scriba TJ, Tameris M, Mansoor N et al. Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants. J. Infect. Dis. 203(12), 1832–1843 (2011).
  • Dunachie SJ, Walther M, Epstein JE et al. A DNA prime-modified vaccinia virus Ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infect. Immun. 74(10), 5933–5942 (2006).
  • Rolland M, Edlefsen PT, Larsen BB et al. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2. Nature 490(7420), 417–420 (2012).
  • Barouch DH, Liu J, Li H et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482(7383), 89–93 (2012).
  • Capone S, Reyes-Sandoval A, Naddeo M et al. Immune responses against a liver-stage malaria antigen induced by simian adenoviral vector AdCh63 and MVA prime–boost immunisation in non-human primates. Vaccine 29(2), 256–265 (2010).
  • Greer CE, Zhou F, Legg HS et al. A chimeric alphavirus RNA replicon gene-based vaccine for human parainfluenza virus type 3 induces protective immunity against intranasal virus challenge. Vaccine 25(3), 481–489 (2007).
  • Thornburg NJ, Ray CA, Collier ML, Liao HX, Pickup DJ, Johnston RE. Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge. Virology 362(2), 441–452 (2007).
  • Davis NL, West A, Reap E et al. Alphavirus replicon particles as candidate HIV vaccines. IUBMB Life 53(4-5), 209–211 (2002).
  • Bernstein DI, Reap EA, Katen K et al. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine 28(2), 484–493 (2009).
  • Wecker M, Gilbert P, Russell N et al.; HVTN 040/059 Protocol Team; NIAID HIV Vaccine Trials Network. Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults. Clin. Vaccine Immunol. 19(10), 1651–1660 (2012).
  • Smith JG, Wiethoff CM, Stewart PL, Nemerow GR. Adenovirus. Curr. Top. Microbiol. Immunol. 343, 195–224 (2010).
  • Draper SJ, Heeney JL. Viruses as vaccine vectors for infectious diseases and cancer. Nat. Rev. Microbiol. 8(1), 62–73 (2010).
  • Catanzaro AT, Koup RA, Roederer M et al.; Vaccine Research Center 006 Study Team. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J. Infect. Dis. 194(12), 1638–1649 (2006).
  • Ledgerwood JE, Costner P, Desai N et al.; VRC 205 Study Team. A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 29(2), 304–313 (2010).
  • Priddy FH, Brown D, Kublin J et al.; Merck V520-016 Study Group. 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(11), 1769–1781 (2008).
  • Graham BS, Koup RA, Roederer M et al.; Vaccine Research Center 004 Study Team. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J. Infect. Dis. 194(12), 1650–1660 (2006).
  • McElrath MJ, De Rosa SC, Moodie Z et al.; Step Study Protocol Team. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372(9653), 1894–1905 (2008).
  • Buchbinder SP, Mehrotra DV, Duerr A et al.; Step Study Protocol Team. 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(9653), 1881–1893 (2008).
  • Gray GE, Allen M, Moodie Z et al.; HVTN 503/Phambili study team. 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(7), 507–515 (2011).
  • Rolland M, Tovanabutra S, deCamp AC et al. Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat. Med. 17(3), 366–371 (2011).
  • Fitzgerald DW, Janes H, Robertson M et al.; Step Study Protocol Team. An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study). J. Infect. Dis. 203(6), 765–772 (2011).
  • Hutnick NA, Carnathan DG, Dubey SA et al. Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat. Med. 15(8), 876–878 (2009).
  • O’Brien KL, Liu J, King SL et al. Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans. Nat. Med. 15(8), 873–875 (2009).
  • Sedegah M, Tamminga C, McGrath S et al. Adenovirus 5-vectored P. falciparum vaccine expressing CSP and AMA1. Part A: safety and immunogenicity in seronegative adults. PLoS ONE 6(10), e24586 (2011).
  • Tamminga C, Sedegah M, Regis D et al. Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component. PLoS ONE 6(10), e25868 (2011).
  • Koup RA, Roederer M, Lamoreaux L et al.; VRC 009 Study Team; VRC 010 Study Team. Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS ONE 5(2), e9015 (2010).
  • Santra S, Seaman MS, Xu L et al. Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates. J. Virol. 79(10), 6516–6522 (2005).
  • Barouch DH, Liu J, Lynch DM et al. Protective efficacy of a single immunization of a chimeric adenovirus vector-based vaccine against simian immunodeficiency virus challenge in rhesus monkeys. J. Virol. 83(18), 9584–9590 (2009).
  • Letvin NL, Mascola JR, Sun Y et al. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312(5779), 1530–1533 (2006).
  • Barouch DH. Novel adenovirus vector-based vaccines for HIV-1. Curr. Opin. HIV AIDS 5(5), 386–390 (2010).
  • Barouch DH, Kik SV, Weverling GJ et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine 29(32), 5203–5209 (2011).
  • Nwanegbo E, Vardas E, Gao W et al. Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States. Clin. Diagn. Lab. Immunol. 11(2), 351–357 (2004).
  • Abbink P, Lemckert AA, Ewald BA et al. Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J. Virol. 81(9), 4654–4663 (2007).
  • Thorner AR, Vogels R, Kaspers J et al. Age dependence of adenovirus-specific neutralizing antibody titers in individuals from sub-Saharan Africa. J. Clin. Microbiol. 44(10), 3781–3783 (2006).
  • Li H, Rhee EG, Masek-Hammerman K, Teigler JE, Abbink P, Barouch DH. Adenovirus serotype 26 utilizes CD46 as a primary cellular receptor and only transiently activates T lymphocytes following vaccination of rhesus monkeys. J. Virol. 86(19), 10862–10865 (2012).
  • Vogels R, Zuijdgeest D, van Rijnsoever R et al. 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(15), 8263–8271 (2003).
  • Waddington SN, McVey JH, Bhella D et al. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 132(3), 397–409 (2008).
  • Liu J, Ewald BA, Lynch DM et al. Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime–boost regimens in rhesus monkeys. J. Virol. 82(10), 4844–4852 (2008).
  • Teigler JE, Iampietro MJ, Barouch DH. Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys. J. Virol. 86(18), 9590–9598 (2012).
  • Colloca S, Barnes E, Folgori A et al. Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species. Sci. Transl. Med. 4(115), 115ra2 (2012).
  • Geisbert TW, Bailey M, Hensley L et al. Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J. Virol. 85(9), 4222–4233 (2011).
  • Liu J, O’Brien KL, Lynch DM et al. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature 457(7225), 87–91 (2009).
  • Keefer MC, Gilmour J, Hayes P et al. 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 7(8), e41936 (2012).
  • Abel B, Tameris M, Mansoor N et al. The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults. Am. J. Respir. Crit. Care Med. 181(12), 1407–1417 (2010).
  • Baden LR, Walsh SR, Seaman MS et al. First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 env vaccine (IPCAVD 001). J. Infect. Dis. 207(2), 240–247 (2013).
  • Dudareva M, Andrews L, Gilbert SC et al. Prevalence of serum neutralizing antibodies against chimpanzee adenovirus 63 and human adenovirus 5 in Kenyan children, in the context of vaccine vector efficacy. Vaccine 27(27), 3501–3504 (2009).
  • Ersching J, Hernandez MI, Cezarotto FS et al. Neutralizing antibodies to human and simian adenoviruses in humans and New-World monkeys. Virology 407(1), 1–6 (2010).
  • Xiang Z, Li Y, Cun A et al. Chimpanzee adenovirus antibodies in humans, sub-Saharan Africa. Emerging Infect. Dis. 12(10), 1596–1599 (2006).
  • Roy S, Medina-Jaszek A, Wilson MJ et al. Creation of a panel of vectors based on ape adenovirus isolates. J. Gene Med. 13(1), 17–25 (2011).
  • Farina SF, Gao GP, Xiang ZQ et al. Replication-defective vector based on a chimpanzee adenovirus. J. Virol. 75(23), 11603–11613 (2001).
  • Dicks MD, Spencer AJ, Edwards NJ et al. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS ONE 7(7), e40385 (2012).
  • Roy S, Vandenberghe LH, Kryazhimskiy S et al. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates. PLoS Pathog. 5(7), e1000503 (2009).
  • Peruzzi D, Dharmapuri S, Cirillo A et al. A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer vaccines. Vaccine 27(9), 1293–1300 (2009).
  • Kobinger GP, Feldmann H, Zhi Y et al. Chimpanzee adenovirus vaccine protects against Zaire Ebola virus. Virology 346(2), 394–401 (2006).
  • Roy S, Kobinger GP, Lin J et al. Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein. Vaccine 25(39–40), 6845–6851 (2007).
  • Reyes-Sandoval A, Sridhar S, Berthoud T et al. Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. Eur. J. Immunol. 38(3), 732–741 (2008).
  • Tatsis N, Lasaro MO, Lin SW et al. Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens. J. Immunol. 182(10), 6587–6599 (2009).
  • de Souza AP, Haut LH, Silva R et al. Genital CD8+ T cell response to HIV-1 gag in mice immunized by mucosal routes with a recombinant simian adenovirus. Vaccine 25(1), 109–116 (2007).
  • Fitzgerald JC, Gao GP, Reyes-Sandoval A et al. A simian replication-defective adenoviral recombinant vaccine to HIV-1 gag. J. Immunol. 170(3), 1416–1422 (2003).
  • Reyes-Sandoval A, Fitzgerald JC, Grant R et al. Human immunodeficiency virus type 1-specific immune responses in primates upon sequential immunization with adenoviral vaccine carriers of human and simian serotypes. J. Virol. 78(14), 7392–7399 (2004).
  • Goodman AL, Epp C, Moss D et al. New candidate vaccines against blood-stage Plasmodium falciparum malaria: prime–boost immunization regimens incorporating human and simian adenoviral vectors and poxviral vectors expressing an optimized antigen based on merozoite surface protein 1. Infect. Immun. 78(11), 4601–4612 (2010).
  • Reyes-Sandoval A, Berthoud T, Alder N et al. Prime–boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses. Infect. Immun. 78(1), 145–153 (2010).
  • Fattori E, Zampaglione I, Arcuri M et al. Efficient immunization of rhesus macaques with an HCV candidate vaccine by heterologous priming–boosting with novel adenoviral vectors based on different serotypes. Gene Ther. 13(14), 1088–1096 (2006).
  • Zhou D, Cun A, Li Y, Xiang Z, Ertl HC. A chimpanzee-origin adenovirus vector expressing the rabies virus glycoprotein as an oral vaccine against inhalation infection with rabies virus. Mol. Ther. 14(5), 662–672 (2006).
  • Zhi Y, Figueredo J, Kobinger GP et al. Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus. Hum. Gene Ther. 17(5), 500–506 (2006).
  • Barnes E, Folgori A, Capone S et al. Novel adenovirus-based vaccines induce broad and sustained T cell responses to HCV in man. Sci. Transl. Med. 4(115), 115ra1 (2012).
  • Sheehy SH, Duncan CJ, Elias SC et al. Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1 in ChAd63 and MVA vaccine vectors. Mol. Ther. 19(12), 2269–2276 (2011).
  • Sheehy SH, Duncan CJ, Elias SC et al. 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(2), e31208 (2012).
  • O’Hara GA, Duncan CJ, Ewer KJ et al. Clinical assessment of a recombinant simian adenovirus ChAd63: a potent new vaccine vector. J. Infect. Dis. 205(5), 772–781 (2012).
  • Lyke KE, Daou M, Diarra I et al. Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: results of a Phase I randomized trial. Vaccine 27(15), 2171–2176 (2009).
  • Duncan CJ, Sheehy SH, Ewer KJ et al. Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909. PLoS ONE 6(7), e22271 (2011).
  • Ellis RD, Martin LB, Shaffer D et al. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naive adults. PLoS ONE 5(1), e8787 (2010).
  • Ellis RD, Mullen GE, Pierce M et al. A Phase 1 study of the blood-stage malaria vaccine candidate AMA1-C1/Alhydrogel with CPG 7909, using two different formulations and dosing intervals. Vaccine 27(31), 4104–4109 (2009).
  • Malkin EM, Diemert DJ, McArthur JH et al. Phase 1 clinical trial of apical membrane antigen 1: an asexual blood-stage vaccine for Plasmodium falciparum malaria. Infect. Immun. 73(6), 3677–3685 (2005).
  • Mullen GE, Ellis RD, Miura K et al. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS ONE 3(8), e2940 (2008).
  • Ogutu BR, Apollo OJ, McKinney D et al.; MSP-1 Malaria Vaccine Working Group. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS ONE 4(3), e4708 (2009).
  • Pierce MA, Ellis RD, Martin LB et al. Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults. Vaccine 28(10), 2236–2242 (2010).
  • Sheehy SH, Duncan CJ, Elias SC et al. ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol. Ther. 20(12), 2355–2368 (2012).
  • Folgori A, Capone S, Ruggeri L et al. A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees. Nat. Med. 12(2), 190–197 (2006).
  • Capone S, Meola A, Ercole BB et al. A novel adenovirus type 6 (Ad6)-based hepatitis C virus vector that overcomes preexisting anti-ad5 immunity and induces potent and broad cellular immune responses in rhesus macaques. J. Virol. 80(4), 1688–1699 (2006).
  • Akondy RS, Monson ND, Miller JD et al. The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J. Immunol. 183(12), 7919–7930 (2009).
  • Hansen SG, Ford JC, Lewis MS et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473(7348), 523–527 (2011).
  • Smith CL, Mirza F, Pasquetto V et al. Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara. J. Immunol. 175(12), 8431–8437 (2005).
  • Clark RH, Kenyon JC, Bartlett NW, Tscharke DC, Smith GL. Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy. J. Gen. Virol. 87(Pt 1), 29–38 (2006).
  • Falivene J, Del Médico Zajac MP, Pascutti MF et al. Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. PLoS ONE 7(2), e32220 (2012).
  • García-Arriaza J, Nájera JL, Gómez CE et al. A candidate HIV/AIDS vaccine (MVA-B) lacking vaccinia virus gene C6L enhances memory HIV-1-specific T-cell responses. PLoS ONE 6(8), e24244 (2011).
  • Staib C, Kisling S, Erfle V, Sutter G. Inactivation of the viral interleukin 1β receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J. Gen. Virol. 86(Pt 7), 1997–2006 (2005).
  • Guzman E, Cubillos-Zapata C, Cottingham MG et al. Modified vaccinia virus Ankara-based vaccine vectors induce apoptosis in dendritic cells draining from the skin via both the extrinsic and intrinsic caspase pathways, preventing efficient antigen presentation. J. Virol. 86(10), 5452–5466 (2012).
  • Hutnick NA, Carnathan DG, Dubey SA et al. Vaccination with Ad5 vectors expands Ad5-specific CD8 T cells without altering memory phenotype or functionality. PLoS ONE 5(12), e14385 (2010).
  • Leen AM, Christin A, Khalil M et al. Identification of hexon-specific CD4 and CD8 T-cell epitopes for vaccine and immunotherapy. J. Virol. 82(1), 546–554 (2008).
  • Leen AM, Sili U, Vanin EF et al. Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells. Blood 104(8), 2432–2440 (2004).
  • Onion D, Crompton LJ, Milligan DW, Moss PA, Lee SP, Mautner V. The CD4+ T-cell response to adenovirus is focused against conserved residues within the hexon protein. J. Gen. Virol. 88(Pt 9), 2417–2425 (2007).
  • Frahm N, DeCamp AC, Friedrich DP et al. Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J. Clin. Invest. 122(1), 359–367 (2012).
  • Hutnick NA, Carnathan D, Demers K, Makedonas G, Ertl HC, Betts MR. Adenovirus-specific human T cells are pervasive, polyfunctional, and cross-reactive. Vaccine 28(8), 1932–1941 (2010).
  • Draper SJ, Biswas S, Spencer AJ et al. Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques by combining adenovirus, poxvirus, and protein-in-adjuvant vaccines. J. Immunol. 185(12), 7583–7595 (2010).
  • Roy S, Gao G, Lu Y et al. Characterization of a family of chimpanzee adenoviruses and development of molecular clones for gene transfer vectors. Hum. Gene Ther. 15(5), 519–530 (2004).
  • Brown SW, Mehtali M. The Avian EB66® cell line, application to vaccines, and therapeutic protein production. PDA J. Pharm. Sci. Technol. 64(5), 419–425 (2010).
  • Kraus B, von Fircks S, Feigl S et al. Avian cell line – technology for large scale vaccine production. BMC Proc. 5(Suppl. 8), P52 (2011).
  • Lohr V, Rath A, Genzel Y, Jordan I, Sandig V, Reichl U. New avian suspension cell lines provide production of influenza virus and MVA in serum-free media: studies on growth, metabolism and virus propagation. Vaccine 27(36), 4975–4982 (2009).
  • Alcock R, Cottingham MG, Rollier CS et al. Long-term thermostabilization of live poxviral and adenoviral vaccine vectors at supraphysiological temperatures in carbohydrate glass. Sci. Transl. Med. 2(19), 19ra12 (2010).
  • Mercier GT, Nehete PN, Passeri MF et al. Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules. Vaccine 25(52), 8687–8701 (2007).
  • Kis EE, Winter G, Myschik J. Devices for intradermal vaccination. Vaccine 30(3), 523–538 (2012).
  • Vrdoljak A, McGrath MG, Carey JB et al. Coated microneedle arrays for transcutaneous delivery of live virus vaccines. J. Control. Release 159(1), 34–42 (2012).
  • Brandtzaeg P. Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways. Am. J. Respir. Crit. Care Med. 183(12), 1595–1604 (2011).
  • Ogra PL, Faden H, Welliver RC. Vaccination strategies for mucosal immune responses. Clin. Microbiol. Rev. 14(2), 430–445 (2001).
  • Renteria SS, Clemens CC, Croyle MA. Development of a nasal adenovirus-based vaccine: effect of concentration and formulation on adenovirus stability and infectious titer during actuation from two delivery devices. Vaccine 28(9), 2137–2148 (2010).
  • Tutykhina IL, Logunov DY, Shcherbinin DN et al. Development of adenoviral vector-based mucosal vaccine against influenza. J. Mol. Med. 89(4), 331–341 (2011).
  • Zhang J, Tarbet EB, Toro H, Tang DC. Adenovirus-vectored drug-vaccine duo as a potential driver for conferring mass protection against infectious diseases. Expert Rev. Vaccines 10(11), 1539–1552 (2011).
  • Van Kampen KR, Shi Z, Gao P et al. Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans. Vaccine 23(8), 1029–1036 (2005).
  • Draper SJ, Biswas S, Spencer AJ et al. Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques by combining adenovirus, poxvirus, and protein-in-adjuvant vaccines. J. Immunol. 185(12), 7583–7595 (2010).
  • Bejon P, Mwacharo J, Kai O et al. A Phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS Clin. Trials 1(6), e29 (2006).
  • Bejon P, Ogada E, Mwangi T et al. Extended follow-up following a Phase 2b randomized trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya. PLoS ONE 2(8), e707 (2007).
  • Moorthy VS, Imoukhuede EB, Milligan P et al. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLoS Med. 1(2), e33 (2004).
  • Rosario M, Bridgeman A, Quakkelaar ED et al. Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques. Eur. J. Immunol. 40(7), 1973–1984 (2010).
  • Ip PP, Nijman HW, Wilschut J, Daemen T. Therapeutic vaccination against chronic hepatitis C virus infection. Antiviral Res. 96(1), 36–50 (2012).

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