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Prime Boost Regimens for Enhancing Immunity: Magnitude, Quality of Mucosal and Systemic Gene Vaccines

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Gene Vaccines

Abstract

The use of therapeutic or prophylactic vaccines against numerous infectious agents has been well documented. The hallmark of most vaccine strategies is to mimic infection and induce immunological memory that has the potential to confer protection. The use of live attenuated viruses, “killed” viruses and recombinant viral proteins for vaccination are classical vaccine approaches that have successfully induced protective antibody and cell mediated immune responses (CMI) against viruses such as small pox, influenza, polio, mumps, measles, and rubella. Despite the successes of classical vaccine approaches, these have been ineffective against chronic and highly pathogenic diseases such as human immunodeficiency virus-1 (HIV-1), tuberculosis (TB) or malaria. Hence, this paved the way for the emergence of range of novel vaccine approaches. In particular, the use of recombinant vector technologies such as the use of recombinant DNA (rDNA) or recombinant live virus vectors encoding single or multiple epitopes used in prime-boost vaccination strategies have exhibited immense potential for generating excellent immunity against intracellular pathogens such as M. tuberculosis, HIV-1, simian immunodeficiency virus (SIV), Plasmodium, Leishmania, S. mansoni, hepatitis C virus, herpes simplex virus and hepatitis B virus. In this chapter, we discuss the use of gene based heterologous prime-boost immunisation strategies for improved vaccination against intracellular pathogens, particularly with respect to HIV-1, given that prime-boost vaccine strategies have been extensively tested and studied against this virus in animal models as well as in humans.

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References

  • Ahmed N, Gottschalk S (2009) How to design effective vaccines: lessons from an old success story. Expert Rev Vaccines 8(5):543–546

    Article  PubMed  CAS  Google Scholar 

  • Alexander-Miller MA (2005) High-avidity CD8+ T cells: optimal soldiers in the war against viruses and tumors. Immunol Res 31(1):13–24

    Article  PubMed  Google Scholar 

  • Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, Bornstein E, Asher TE, Samri A, Schnuriger A, Theodorou I, Costagliola D, Rouzioux C, Agut H, Marcelin AG, Douek D, Autran B, Appay V (2007) Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 204(10):2473–2485

    Article  PubMed  CAS  Google Scholar 

  • Amara RR, Villinger F, Altman JD, Lydy SL, O’Neil SP, Staprans SI, Montefiori DC, Xu Y, Herndon JG, Wyatt LS, Candido MA, Kozyr NL, Earl PL, Smith JM, Ma HL, Grimm BD, Hulsey ML, Miller J, McClure HM, McNicholl JM, Moss B, Robinson HL (2001) Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292(5514):69–74

    Article  PubMed  CAS  Google Scholar 

  • Anderson RJ, Hannan CM, Gilbert SC, Laidlaw SM, Sheu EG, Korten S, Sinden R, Butcher GA, Skinner MA, Hill AV, Dunachie SJ (2004) Enhanced CD8+ T cell immune responses and protection elicited against Plasmodium berghei malaria by prime boost immunization regimens using a novel attenuated fowlpox virus prime-boost strategies for malaria vaccine development. J Immunol 172(5):3094–3100

    PubMed  CAS  Google Scholar 

  • Barouch DH, Kunstman J, Kuroda MJ, Schmitz JE, Santra S, Peyerl FW, Krivulka GR, Beaudry K, Lifton MA, Gorgone DA, Montefiori DC, Lewis MG, Wolinsky SM, Letvin NL (2002) Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature 415(6869):335–339

    Article  PubMed  CAS  Google Scholar 

  • Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220(4599):868–871

    Article  PubMed  CAS  Google Scholar 

  • Belyakov IM, Ahlers JD (2009a) Comment on “trafficking of antigen-specific CD8+ T lymphocytes to mucosal surfaces following intramuscular vaccination”. J Immunol 182(4):1779; author reply 1779–1780

    Article  Google Scholar 

  • Belyakov IM, Ahlers JD (2009b) What role does the route of immunization play in the generation of protective immunity against mucosal pathogens? J Immunol 183(11):6883–6892

    Article  PubMed  CAS  Google Scholar 

  • Belyakov IM, Moss B, Strober W, Berzofsky JA (1999) Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity. Proc Natl Acad Sci USA 96(8):4512–4517

    Article  PubMed  CAS  Google Scholar 

  • Belyakov IM, Hel Z, Kelsall B, Kuznetsov VA, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham PD, Clements JD, Genoveffa F, Srober W, Berzofsky JA (2001) Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med 7(12):1320–1326

    Article  PubMed  CAS  Google Scholar 

  • Belyakov IM, Kuznetsov VA, Kelsall B, Klinman D, Moniuszko M, Lemon M, Markham PD, Pal R, Clements JD, Lewis MG, Strober W, Franchini G, Berzofsky JA (2006) Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood 107(8):3258–3264

    Article  PubMed  CAS  Google Scholar 

  • Bihl F, Frahm N, Di Giammarino L, Sidney J, John M, Yusim K, Woodberry T, Sango K, Hewitt HS, Henry L, Linde CH, Chisholm JV 3rd, Zaman TM, Pae E, Mallal S, Walker BD, Sette A, Korber BT, Heckerman D, Brander C (2006) Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses. J Immunol 176(7):4094–4101

    PubMed  CAS  Google Scholar 

  • Bowman EP, Kuklin NA, Youngman KR, Lazarus NH, Kunkel EJ, Pan J, Greenberg HB, Butcher EC (2002) The intestinal chemokine thymus-expressed chemokine (CCL25) attracts IgA antibody-secreting cells. J Exp Med 195(2):269–275

    Article  PubMed  CAS  Google Scholar 

  • Boyer JD, Ugen KE, Wang B, Agadjanyan M, Gilbert L, Bagarazzi ML, Chattergoon M, Frost P, Javadian A, Williams WV, Refaeli Y, Ciccarelli RB, McCallus D, Coney L, Weiner DB (1997) Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Nat Med 3(5):526

    Article  PubMed  CAS  Google Scholar 

  • Boyer JD, Kim J, Ugen K, Cohen AD, Ahn L, Schumann K, Lacy K, Bagarazzi ML, Javadian A, Ciccarelli RB, Ginsberg RS, MacGregor RR, Weiner DB, Kim JJ, Nottingham LK, Sin JI, Tsai A, Morrison L, Oh J, Dang K, Hu Y, Kazahaya K, Bennett M, Dentchev T, Wilson DM, Chalian AA, Agadjanyan MG (1999) HIV-1 DNA vaccines and chemokines. Vaccine 17(Suppl 2):S53–S64

    Article  PubMed  CAS  Google Scholar 

  • Boyer JD, Robinson TM, Kutzler MA, Parkinson R, Calarota SA, Sidhu MK, Muthumani K, Lewis M, Pavlakis G, Felber B, Weiner D (2005) SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. J Med Primatol 34(5–6):262–270

    Article  PubMed  CAS  Google Scholar 

  • Brave A, Nystrom S, Roos AK, Applequist SE (2010) Plasmid DNA vaccination using skin electroporation promotes poly-functional CD4 T-cell responses. Immunol Cell Biol 89:492–496

    Article  PubMed  CAS  Google Scholar 

  • Broder S, Gallo RC (1984) A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med 311(20):1292–1297

    Article  PubMed  CAS  Google Scholar 

  • Buchan S, Gronevik E, Mathiesen I, King CA, Stevenson FK, Rice J (2005) Electroporation as a “prime/boost” strategy for naked DNA vaccination against a tumor antigen. J Immunol 174(10):6292–6298

    PubMed  CAS  Google Scholar 

  • Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN (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(9653):1881–1893

    Article  PubMed  CAS  Google Scholar 

  • Cai H, Yu DH, Hu XD, Li SX, Zhu YX (2006) A combined DNA vaccine-prime, BCG-boost strategy results in better protection against Mycobacterium bovis challenge. DNA Cell Biol 25(8):438–447

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti BK, Ling X, Yang ZY, Montefiori DC, Panet A, Kong WP, Welcher B, Louder MK, Mascola JR, Nabel GJ (2005) Expanded breadth of virus neutralization after immunization with a multiclade envelope HIV vaccine candidate. Vaccine 23(26):3434–3445

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Prow TW, Crichton ML, Jenkins DW, Roberts MS, Frazer IH, Fernando GJ, Kendall MA (2009) Dry-coated microprojection array patches for targeted delivery of immunotherapeutics to the skin. J Control Release 139(3):212–220, Epub 2009 Jul 2003

    Article  PubMed  CAS  Google Scholar 

  • Corbett M, Bogers WM, Heeney JL, Gerber S, Genin C, Didierlaurent A, Oostermeijer H, Dubbes R, Braskamp G, Lerondel S, Gomez CE, Esteban M, Wagner R, Kondova I, Mooij P, Balla-Jhagjhoorsingh S, Beenhakker N, Koopman G, van der Burg S, Kraehenbuhl JP, Le Pape A (2008) Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic. Proc Natl Acad Sci USA 105(6):2046–2051, Epub 2008 Feb 2011

    Article  PubMed  CAS  Google Scholar 

  • Coupar BEH, Purcell DFJ, Thomson SA, Ramshaw IA, Kent SJ, Boyle DB (2006) Fowlpox virus vaccines for HIV and SIV clinical and pre-clinical trials. Vaccine 24(9):1378–1388

    Article  PubMed  CAS  Google Scholar 

  • Cox E, Verdonck F, Vanrompay D, Goddeeris B (2006) Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa. Vet Res 37(3):511–539, Epub 2006 Apr 2014

    Article  PubMed  CAS  Google Scholar 

  • Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13(7):843–850, Epub 2007 Jun 2010

    Article  PubMed  CAS  Google Scholar 

  • Day SL, Ramshaw IA, Ramsay AJ, Ranasinghe C (2008) Differential effects of the type I interferons alpha4, beta, and epsilon on antiviral activity and vaccine efficacy. J Immunol 180(11):7158–7166

    PubMed  CAS  Google Scholar 

  • De Rose R, Sullivan MT, Dale CJ, Kelleher AD, Emery S, Cooper DA, Ramshaw IA, Boyle DB, Kent SJ (2006) Dose-response relationship of DNA and recombinant fowlpox virus prime-boost HIV vaccines: implications for future trials. Hum Vaccines 2(3):134–136

    Google Scholar 

  • Demberg T, Boyer JD, Malkevich N, Patterson LJ, Venzon D, Summers EL, Kalisz I, Kalyanaraman VS, Lee EM, Weiner DB, Robert-Guroff M (2008) Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge. J Virol 82(21):10911–10921, Epub 12008 Aug 10927

    Article  PubMed  CAS  Google Scholar 

  • Derby M, Alexander-Miller M, Tse R, Berzofsky J (2001) High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL. J Immunol 166(3):1690–1697

    PubMed  CAS  Google Scholar 

  • Dormitzer PR, Ulmer JB, Rappuoli R (2008) Structure-based antigen design: a strategy for next generation vaccines. Trends Biotechnol 26(12):659–667

    Article  PubMed  CAS  Google Scholar 

  • Duvall MG, Jaye A, Dong T, Brenchley JM, Alabi AS, Jeffries DJ, van der Sande M, Togun TO, McConkey SJ, Douek DC, McMichael AJ, Whittle HC, Koup RA, Rowland-Jones SL (2006) Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection. J Immunol 176(11):6973–6981

    PubMed  CAS  Google Scholar 

  • Dzutsev AH, Belyakov IM, Isakov DV, Margulies DH, Berzofsky JA (2007) Avidity of CD8 T cells sharpens immunodominance. Int Immunol 19(4):497–507

    Article  PubMed  CAS  Google Scholar 

  • Epstein JE, Charoenvit Y, Kester KE, Wang R, Newcomer R, Fitzpatrick S, Richie TL, Tornieporth N, Heppner DG, Ockenhouse C, Majam V, Holland C, Abot E, Ganeshan H, Berzins M, Jones T, Freydberg CN, Ng J, Norman J, Carucci DJ, Cohen J, Hoffman SL (2004) Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA ­vaccine followed by the recombinant protein vaccine RTS, S/AS02A. Vaccine 22(13–14):1592–1603

    Article  PubMed  CAS  Google Scholar 

  • Estcourt MJ, Ramsay AJ, Brooks A, Thomson SA, Medveckzy CJ, Ramshaw IA (2002) Prime-boost immunization generates a high frequency, high-avidity CD8(+) cytotoxic T lymphocyte population. Int Immunol 14(1):31–37

    Article  PubMed  CAS  Google Scholar 

  • Ferre AL, Hunt PW, Critchfield JW, Young DH, Morris MM, Garcia JC, Pollard RB, Yee HF Jr, Martin JN, Deeks SG, Shacklett BL (2009) Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control. Blood 113(17):3978–3989, Epub 2008 Dec 3923

    Article  PubMed  CAS  Google Scholar 

  • Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF (2005) Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 191(5):654–665

    Article  PubMed  Google Scholar 

  • Fuller DH, Haynes JR (1994) A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. AIDS Res Hum Retrovirus 10(11):1433–1441

    Article  CAS  Google Scholar 

  • Garcia-Hernandez Mde L, Gray A, Hubby B, Kast WM (2007) In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for treating prostate cancer. Cancer Res 67(3):1344–1351

    Article  PubMed  Google Scholar 

  • Gherardi MM, Ramirez JC, Esteban M (2000) Interleukin-12 (IL-12) enhancement of the cellular immune response against human immunodeficiency virus type 1 env antigen in a DNA prime/vaccinia virus boost vaccine regimen is time and dose dependent: suppressive effects of IL-12 boost are mediated by nitric oxide. J Virol 74(14):6278–6286

    Article  PubMed  CAS  Google Scholar 

  • Gherardi MM, Najera JL, Perez-Jimenez E, Guerra S, Garcia-Sastre A, Esteban M (2003) Prime-boost immunisation schedules based on influenza virus and vaccinia virus vectors potentiate cellulare immune responses against human immunodeficiency virus Env proteins systemically and in genitorectal draining lymph nodes. J Virol 77(12):7048–7057

    Article  PubMed  CAS  Google Scholar 

  • Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV (2003) Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol 171(3):1602–1609

    PubMed  CAS  Google Scholar 

  • Gupta RK (1998) Aluminum compounds as vaccine adjuvants. Adv Drug Deliv Rev 32(3):155–172

    Article  PubMed  CAS  Google Scholar 

  • Gurunathan S, Stobie L, Prussin C, Sacks DL, Glaichenhaus N, Fowell DJ, Locksley RM, Chang JT, Wu C-Y, Seder RA (2000) Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells. J Immunol 165:915–924

    PubMed  CAS  Google Scholar 

  • Hagiwara Y, Kawamura YI, Kataoka K, Rahima B, Jackson RJ, Komase K, Dohi T, Boyaka PN, Takeda Y, Kiyono H, McGhee JR, Fujihashi K (2006) A second generation of double mutant cholera toxin adjuvants: enhanced immunity without intracellular trafficking. J Immunol 177(5):3045–3054

    PubMed  CAS  Google Scholar 

  • Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, Legasse AW, Axthelm MK, Oswald K, Trubey CM, Piatak M Jr, Lifson JD, Nelson JA, Jarvis MA, Picker LJ (2009) Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med 15(3):293–299

    Article  PubMed  CAS  Google Scholar 

  • Harding CV, Song R (1994) Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J Immunol 153(11):4925–4933

    PubMed  CAS  Google Scholar 

  • Harrison JM, Bertram EM, Boyle DB, Coupar BE, Ranasinghe C, Ramshaw IA (2006) 4-1BBL coexpression enhances HIV-specific CD8 T cell memory in a poxvirus prime-boost vaccine. Vaccine 24(47–48):6867–6874

    Article  PubMed  CAS  Google Scholar 

  • Hill AV, Reece W, Gothard P, Moorthy V, Roberts M, Flanagan K, Plebanski M, Hannan C, Hu JT, Anderson R, Degano P, Schneider J, Prieur E, Sheu E, Gilbert SC (2000) DNA-based vaccines for malaria: a heterologous prime-boost immunisation strategy. Dev Biol (Basel) 104:171–179

    CAS  Google Scholar 

  • Hutchings CL, Gilbert SC, Hill AV, Moore AC (2005) Novel protein and poxvirus-based vaccine combinations for simultaneous induction of humoral and cell-mediated immunity. J Immunol 175(1):599–606

    PubMed  CAS  Google Scholar 

  • Imrie A, Meeks J, Gurary A, Sukhbataar M, Kitsutani P, Effler P, Zhao Z (2007) Differential functional avidity of dengue virus-specific T-cell clones for variant peptides representing heterologous and previously encountered serotypes. J Virol 81(18):10081–10091

    Article  PubMed  CAS  Google Scholar 

  • Kallenius G, Pawlowski A, Brandtzaeg P, Svenson S (2007) Should a new tuberculosis vaccine be administered intranasally? Tuberculosis (Edinb) 87(4):257–266, Epub 2007 Feb 2026

    Article  CAS  Google Scholar 

  • Kantele A, Hakkinen M, Moldoveanu Z, Lu A, Savilahti E, Alvarez RD, Michalek S, Mestecky J (1998) Differences in immune responses induced by oral and rectal immunizations with Salmonella typhi Ty21a: evidence for compartmentalization within the common mucosal immune system in humans. Infect Immun 66(12):5630–5635

    PubMed  CAS  Google Scholar 

  • Kaufman DR, Liu J, Carville A, Mansfield KG, Havenga MJ, Goudsmit J, Barouch DH (2008) Trafficking of antigen-specific CD8+ T lymphocytes to mucosal surfaces following intramuscular vaccination. J Immunol 181(6):4188–4198

    PubMed  CAS  Google Scholar 

  • Kaul R, Plummer FA, Kimani J, Dong T, Kiama P, Rostron T, Njagi E, MacDonald KS, Bwayo JJ, McMichael AJ, Rowland-Jones SL (2000) HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi. J Immunol 164:1602–1611

    PubMed  CAS  Google Scholar 

  • Kelleher AD, Puls RL, Bebbington M, Boyle D, Ffrench R, Kent SJ, Kippax S, Purcell DFJ, Thomson S, Wand H, Cooper DA, Emery S (2006) A randomised, placebo-controlled phase I trial of DNA prime, recombinant fowlpox virus boost prophylactic vaccine for HIV-1. AIDS 20(2):294–297

    Article  PubMed  CAS  Google Scholar 

  • Kelso A, Groves P (1997) A single peripheral CD8+ T cell can give rise to progeny expressing type 1 and/or type 2 cytokine genes and can retain its multipotentiality through many cell divisions. Proc Natl Acad Sci USA 94(15):8070–8075

    Article  PubMed  CAS  Google Scholar 

  • Kent SJ, Zhao A, Best SJ, Chandler JD, Boyle DB, Ramshaw IA (1998) Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J Virol 72(12):10180–10188

    PubMed  CAS  Google Scholar 

  • Kent SJ, Dale CJ, Ranasinghe C, Stratov I, De Rose R, Chea S, Montefiori DC, Thomson S, Ramshaw IA, Coupar BE, Boyle DB, Law M, Wilson KM, Ramsay AJ (2005) Mucosally-administered human-simian immunodeficiency virus DNA and fowlpox virus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIV(SF162P3). Vaccine 23:5009–5021

    Article  PubMed  CAS  Google Scholar 

  • Kienzle N, Baz A, Kelso A (2004) Profiling the CD8low phenotype, an alternative career choice for CD8 T cells during primary differentiation. Immunol Cell Biol 82(1):75–83

    Article  PubMed  CAS  Google Scholar 

  • Kiyono H, Fukuyama S (2004) NALT- versus Peyer’s-patch mediated mucosal immunity. Nat Immunol 4:699–710

    Article  CAS  Google Scholar 

  • Klavinskis LS, Barnfield C, Gao L, Parker S (1999) Intranasal immunization with plasmid DNA-lipid complexes elicits mucosal immunity in the female genital and rectal tracts. J Immunol 162(1):254–262

    PubMed  CAS  Google Scholar 

  • Kolibab K, Yang A, Derrick SC, Waldmann TA, Perera LP, Morris SL (2010) Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant. Clin Vaccine Immunol 17(5):793–801

    Article  PubMed  CAS  Google Scholar 

  • Kozlowski PA, Neutra MR (2003) The role of mucosal immunity in prevention of HIV transmission. Curr Mol Med 3(3):217–228

    Article  PubMed  CAS  Google Scholar 

  • Kutzler MA, Robinson TM, Chattergoon MA, Choo DK, Choo AY, Choe PY, Ramanathan MP, Parkinson R, Kudchodkar S, Tamura Y, Sidhu M, Roopchand V, Kim JJ, Pavlakis GN, Felber BK, Waldmann TA, Boyer JD, Weiner DB (2005) Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 175(1):112–123

    PubMed  CAS  Google Scholar 

  • Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393(6686):648–659

    Article  PubMed  CAS  Google Scholar 

  • La Gruta NL, Turner SJ, Doherty PC (2004) Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity. J Immunol 172(9):5553–5560

    PubMed  Google Scholar 

  • Lane JM, Ruben FL, Neff JM, Millar JD (1969) Complications of smallpox vaccination. N Engl J Med 281(22):1201–1208

    Article  PubMed  CAS  Google Scholar 

  • Leong KH, Ramsay AJ, Boyle DB, Ramshaw IA (1994) Selective induction of immune responses by cytokines coexpressed in recombinant fowlpox virus. J Virol 68(12):8125–8130

    PubMed  CAS  Google Scholar 

  • Leong KH, Ramsay AJ, Morin MJ, Robinson HL, Boyle DB, Ramshaw IA (1995) Molecular approaches to the control of infectious diseases. In: Brown F, Chanock H, Norrby E (eds) Vaccine 95. Cold Spring Harbor Laboratory, New York, pp 327–331

    Google Scholar 

  • Lillard JW Jr, Boyaka PN, Taub DD, McGhee JR (2001) RANTES potentiates antigen-specific mucosal immune responses. J Immunol 166(1):162–169

    PubMed  CAS  Google Scholar 

  • Liu J, Yu Q, Stone GW, Yue FY, Ngai N, Jones RB, Kornbluth RS, Ostrowski MA (2008) CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals. Vaccine 26(32):4062–4072, Epub 2008 Jun 4062

    Article  PubMed  CAS  Google Scholar 

  • Mascola JR, Montefiori DC (2010) The role of antibodies in HIV vaccines. Annu Rev Immunol 28:413–444

    Article  PubMed  CAS  Google Scholar 

  • McConkey SJ, Reece WH, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV (2003) Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 9(6):729–735

    Article  PubMed  CAS  Google Scholar 

  • McCormack S, Stohr W, Barber T, Bart PA, Harari A, Moog C, Ciuffreda D, Cellerai C, Cowen M, Gamboni R, Burnet S, Legg K, Brodnicki E, Wolf H, Wagner R, Heeney J, Frachette MJ, Tartaglia J, Babiker A, Pantaleo G, Weber J, Harari A, Bart PA, Stohr W, Tapia G, Garcia M, Medjitna-Rais E, Burnet S, Cellerai C, Erlwein O, Barber T, Moog C, Liljestrom P, Wagner R, Wolf H, Kraehenbuhl JP, Esteban M, Heeney J, Frachette MJ, Tartaglia J, McCormack S, Babiker A, Weber J, Pantaleo G (2008) EV02: a Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime-NYVAC-C boost to NYVAC-C alone. Vaccine 26(25):3162–3174, Epub 2008 May 3166

    Article  PubMed  CAS  Google Scholar 

  • McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF (2010) The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 10(1):11–23

    Article  PubMed  CAS  Google Scholar 

  • Moorthy VS, Imoukhuede EB, Keating S, Pinder M, Webster D, Skinner MA, Gilbert SC, Walraven G, Hill AV (2004) Phase 1 evaluation of 3 highly immunogenic prime-boost regimens, including a 12-month reboosting vaccination, for malaria vaccination in Gambian men. J Infect Dis 189(12):2213–2219, Epub 2004 May 2224

    Article  PubMed  CAS  Google Scholar 

  • Musey L, Hu Y, Eckert L, Christensen M, Karchmer T, McElrath MJ (1997) HIV-1 induces cytotoxic T lymphocytes in the cervix of infected women. J Exp Med 185(2):293–303

    Article  PubMed  CAS  Google Scholar 

  • Ogra P (1999) Mucosal immunity, 2nd edn. Academic Press, San Diego, CA

    Google Scholar 

  • Ogra PL, Faden H, Welliver RC (2001) Vaccination strategies for mucosal immune responses. Clin Microbiol Rev 14(2):430–445

    Article  PubMed  CAS  Google Scholar 

  • Oh S, Hodge JW, Ahlers JD, Burke DS, Schlom J, Berzofsky JA (2003) Selective induction of high avidity CTL by altering the balance of signals from APC. J Immunol 170(5):2523–2530

    PubMed  CAS  Google Scholar 

  • Osborn JE (1995) HIV: the more things change, the more they stay the same. Nat Med 1(10):991–993

    Article  PubMed  CAS  Google Scholar 

  • Pal R, Venzon D, Santra S, Kalyanaraman VS, Montefiori DC, Hocker L, Hudacik L, Rose N, Nacsa J, Edghill-Smith Y, Moniuszko M, Hel Z, Belyakov IM, Berzofsky JA, Parks RW, Markham PD, Letvin NL, Tartaglia J, Franchini G (2006) Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels. J Virol 80(8):3732–3742

    Article  PubMed  CAS  Google Scholar 

  • Perez-Jimenez E, Kochan G, Gherardi MM, Esteban M (2006) MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis. Microbes Infect 8(3):810–822, Epub 2006 Jan 2013

    Article  PubMed  CAS  Google Scholar 

  • Perrone LA, Ahmad A, Veguilla V, Lu X, Smith G, Katz JM, Pushko P, Tumpey TM (2009) Intranasal vaccination with 1918 influenza virus-like particles protects mice and ferrets from lethal 1918 and H5N1 influenza virus challenge. J Virol 83(11):5726–5734

    Article  PubMed  CAS  Google Scholar 

  • Pitisuttithum P (2005) HIV-1 prophylactic vaccine trials in Thailand. Curr HIV Res 3(1):17–30

    Article  PubMed  CAS  Google Scholar 

  • Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, Hu D, Tappero JW, Choopanya K (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(12):1661–1671

    Article  PubMed  CAS  Google Scholar 

  • Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, Lalezari J, Santiago S, Marmor M, Lally M, Novak RM, Brown SJ, Kulkarni P, Dubey SA, Kierstead LS, Casimiro DR, Mogg R, DiNubile MJ, Shiver JW, Leavitt RY, Robertson MN, Mehrotra DV, Quirk E (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(11):1769–1781

    Article  PubMed  CAS  Google Scholar 

  • Ramsay AJ, Leong KH, Ramshaw IA (1997) DNA vaccination against virus infection and enhancement of antiviral immunity following consecutive immunization with DNA and viral vectors. Immunol Cell Biol 75(4):382–388

    Article  PubMed  CAS  Google Scholar 

  • Ramsay AJ, Kent SJ, Strugnell RA, Suhrbier A, Thomson SA, Ramshaw IA (1999) Genetic vaccination strategies for enhanced cellular, humoral and mucosal immunity. Immunol Rev 171:27–44

    Article  PubMed  CAS  Google Scholar 

  • Ramshaw IA, Ramsay AJ (2000) The prime-boost strategy: exciting prospects for improved vaccination. Immunol Today 21(4):163–165

    Article  PubMed  CAS  Google Scholar 

  • Ranasinghe C, Ramshaw IA (2009a) Genetic heterologous prime-boost vaccination strategies for improved systemic and mucosal immunity. Expert Rev Vaccines 8(9):1171–1181

    Article  PubMed  CAS  Google Scholar 

  • Ranasinghe C, Ramshaw IA (2009b) Immunisation route-dependent expression of IL-4/IL-13 can modulate HIV-specific CD8(+) CTL avidity. Eur J Immunol 39(7):1819–1830

    Article  PubMed  CAS  Google Scholar 

  • Ranasinghe C, Medveczky JC, Woltring D, Gao K, Thomson S, Coupar BE, Boyle DB, Ramsay AJ, Ramshaw IA (2006) Evaluation of fowlpox-vaccinia virus prime-boost vaccine strategies for high-level mucosal and systemic immunity against HIV-1. Vaccine 24(31–32):5881–5895

    Article  PubMed  CAS  Google Scholar 

  • Ranasinghe C, Turner SJ, McArthur C, Sutherland DB, Kim JH, Doherty PC, Ramshaw IA (2007) Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles. J Immunol 178(4):2370–2379

    PubMed  CAS  Google Scholar 

  • Reece JC, Loh L, Alcantara S, Fernandez CS, Stambas J, Sexton A, De Rose R, Petravic J, Davenport MP, Kent SJ (2010) Timing of immune escape linked to success or failure of vaccination. PLoS 5(9), (pii):e12774

    Google Scholar 

  • Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361(23):2209–2220

    Article  PubMed  CAS  Google Scholar 

  • Roberts JD, Bebenek K, Kunkel TA (1988) The accuracy of reverse transcriptase from HIV-1. Science 242(4882):1171–1173

    Article  PubMed  CAS  Google Scholar 

  • Robinson HL, Montefiori DC, Johnson RP, Manson KH, Kalish ML, Lifson JD, Rizvi TA, Lu S, Hu SL, Mazzara GP, Panicali DL, Herndon JG, Glickman R, Candido MA, Lydy SL, Wyand MS, McClure HM (1999) Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat Med 5(5):526–534

    Article  PubMed  CAS  Google Scholar 

  • Rollman E, Brave A, Boberg A, Gudmundsdotter L, Engstrom G, Isaguliants M, Ljungberg K, Lundgren B, Blomberg P, Hinkula J, Hejdeman B, Sandstrom E, Liu M, Wahren B (2005) The rationale behind a vaccine based on multiple HIV antigens. Microbes Infect 7(14):1414–1423

    PubMed  CAS  Google Scholar 

  • Santosuosso M, Zhang X, McCormick S, Wang J, Hitt M, Xing Z (2005) Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen. J Immunol 174(12):7986–7994

    PubMed  CAS  Google Scholar 

  • Seder RA, Darrah PA, Roederer M (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8(4):247–258

    Article  PubMed  CAS  Google Scholar 

  • Sekaly RP (2008) The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development? J Exp Med 205(1):7–12, Epub 2008 Jan 2014

    Article  PubMed  CAS  Google Scholar 

  • Seppala IJ, Makela O (1984) Adjuvant effect of bacterial LPS and/or alum precipitation in responses to polysaccharide and protein antigens. Immunology 53(4):827–836

    PubMed  CAS  Google Scholar 

  • Shiver JW, Fu T-M, Chen L, Casimiro DR, Davies M-E, Evans RK, Zhang Z-Q, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schlief WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA (2002) Replication-incompetent adenivoral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331–335

    Article  PubMed  CAS  Google Scholar 

  • Skinner MA, Buddle BM, Wedlock DN, Keen D, de Lisle GW, Tascon RE, Ferraz JC, Lowrie DB, Cockle PJ, Vordermeier HM, Hewinson RG (2003) A DNA prime-Mycobacterium bovis BCG boost vaccination strategy for cattle induces protection against bovine tuberculosis. Infect Immun 71(9):4901–4907

    Article  PubMed  CAS  Google Scholar 

  • Spellberg B, Edwards JE Jr (2001) Type 1/type 2 immunity in infectious diseases. Clin Infect Dis 32(1):76–102

    Article  PubMed  CAS  Google Scholar 

  • Staerz UD, Karasuyama H, Garner AM (1987) Cytotoxic T lymphocytes against a soluble protein. Nature 329(6138):449–451

    Article  PubMed  CAS  Google Scholar 

  • Stambas J, Brown SA, Gutierrez A, Sealy R, Yue W, Jones B, Lockey TD, Zirkel A, Freiden P, Brown B, Surman S, Coleclough C, Slobod KS, Doherty PC, Hurwitz JL (2005) Long lived multi-isotype anti-HIV antibody responses following a prime-double boost immunization strategy. Vaccine 23(19):2454–2464

    Article  PubMed  CAS  Google Scholar 

  • Tapia E, Perez-Jimenez E, Lopez-Fuertes L, Gonzalo R, Gherardi MM, Esteban M (2003) The combination of DNA vectors expressing IL-12  +  IL-18 elicits high protective immune response against cutaneous leishmaniasis after priming with DNA-p36/LACK and the cytokines, followed by a booster with a vaccinia virus recombinant expressing p36/LACK. Microbes Infect 5(2):73–84

    Article  PubMed  CAS  Google Scholar 

  • Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, Rosenzweig M, Johnson RP, Desrosiers RC, Lackner AA (1998) Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280(5362):427–431

    Article  PubMed  CAS  Google Scholar 

  • Veazey RS, Gauduin MC, Mansfield KG, Tham IC, Altman JD, Lifson JD, Lackner AA, Johnson RP (2001) Emergence and kinetics of simian immunodeficiency virus-specific CD8(+) T cells in the intestines of macaques during primary infection. J Virol 75(21):10515–10519

    Article  PubMed  CAS  Google Scholar 

  • Vordermeier HM, Villarreal-Ramos B, Cockle PJ, McAulay M, Rhodes SG, Thacker T, Gilbert SC, McShane H, Hill AV, Xing Z, Hewinson RG (2009) Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis. Infect Immun 77(8):3364–3373, Epub 2009 Jun 3361

    Article  PubMed  CAS  Google Scholar 

  • Wagner N, Lohler J, Kunkel EJ, Ley K, Leung E, Krissansen G, Rajewsky K, Muller W (1996) Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature 382(6589):366–370

    Article  PubMed  CAS  Google Scholar 

  • Wallace M, Evans B, Woods S, Mogg R, Zhang L, Finnefrock AC, Rabussay D, Fons M, Mallee J, Mehrotra D, Schodel F, Musey L (2009) Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults. Mol Ther 17(5):922–928, Epub 2009 Mar 2010

    Article  PubMed  CAS  Google Scholar 

  • Williams A, Hatch GJ, Clark SO, Gooch KE, Hatch KA, Hall GA, Huygen K, Ottenhoff TH, Franken KL, Andersen P, Doherty TM, Kaufmann SH, Grode L, Seiler P, Martin C, Gicquel B, Cole ST, Brodin P, Pym AS, Dalemans W, Cohen J, Lobet Y, Goonetilleke N, McShane H, Hill A, Parish T, Smith D, Stoker NG, Lowrie DB, Kallenius G, Svenson S, Pawlowski A, Blake K, Marsh PD (2005) Evaluation of vaccines in the EU TB vaccine cluster using a guinea pig aerosol infection model of tuberculosis. Tuberculosis (Edinb) 85(1–2):29–38, Epub 2005 Jan 2020

    Article  CAS  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247(4949 Pt 1):1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Wright PF, Mestecky J, McElrath MJ, Keefer MC, Gorse GJ, Goepfert PA, Moldoveanu Z, Schwartz D, Spearman PW, El Habib R, Spring MD, Zhu Y, Smith C, Flores J, Weinhold KJ (2004) Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. J Infect Dis 189(7):1221–1231, Epub 2004 Mar 1215

    Article  PubMed  CAS  Google Scholar 

  • Xiang ZQ, Pasquini S, Ertl HCJ (1999) Induction of genital immunity by DNA priming and intranasal booster immunisation with a replication-defective adenoviral recombinant. J Immunol 162:6716–6723

    PubMed  CAS  Google Scholar 

  • Yang K, Whalen BJ, Tirabassi RS, Selin LK, Levchenko TS, Torchilin VP, Kislauskis EH, Guberski DL (2008) A DNA vaccine prime followed by a liposome-encapsulated protein boost confers enhanced mucosal immune responses and protection. J Immunol 180(9):6159–6167

    PubMed  CAS  Google Scholar 

  • Zhong L, Granelli-Piperno A, Choi Y, Steinman RM (1999) Recombinant adenovirus is an efficient and non-perturbing genetic vector for human dendritic cells. Eur J Immunol 29(3):964–972

    Article  PubMed  CAS  Google Scholar 

  • Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Do Kwon Y, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD (2010) Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329(5993):811–817

    Article  PubMed  CAS  Google Scholar 

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Financial Disclosure/Acknowledgements

This work and CR was supported by The Australian National Health and Medical Research Council project grant award 525431 (CR)

Conflict of interest:The authors declare no financial or commercial conflict of interest.

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Authors and Affiliations

  1. Department of Emerging Pathogens and Vaccines, Molecular Mucosal Vaccine Immunology Group, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia

    Danushka K. Wijesundara

  2. Department of Immunology, Molecular Mucosal Vaccine Immunology Group The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia

    Charani Ranasinghe

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  1. Danushka K. Wijesundara
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Correspondence to Charani Ranasinghe .

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  1. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Josef Thalhamer

  2. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Richard Weiss

  3. , Department of Molecular Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Sandra Scheiblhofer

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Wijesundara, D.K., Ranasinghe, C. (2012). Prime Boost Regimens for Enhancing Immunity: Magnitude, Quality of Mucosal and Systemic Gene Vaccines. In: Thalhamer, J., Weiss, R., Scheiblhofer, S. (eds) Gene Vaccines. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0439-2_9

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