The advantages of genetic immunization of the new vaccine using plasmid DNAs are multifold. For example, it is easy to generate plasmid DNAs, increase their dose during the manufacturing process, and sterilize them. Furthermore, they can be stored for a long period of time upon stabilization, and their protein encoding sequences can be easily modified by employing various DNA-manipulation techniques. Although DNA vaccinations strongly increase Th1-mediated immune responses in animals, several problems persist. One is about their weak immunogenicity in humans. To overcome this problem, various genetic adjuvants, electroporation, and prime-boost methods have been developed preclinically, which are reviewed here.
References
[1]
Alarcon, J.B.; Waine, G.W.; McManus, D.P. DNA vaccines: Technology and application as anti-parasite and anti-microbial agents. Adv. Parasitol. 1999, 42, 343–410.
[2]
Bins, A.D.; van den Berg, J.H.; Oosterhuis, K.; Haanen, J.B. Recent advances towards the clinical application of DNA vaccines. Neth. J. Med. 2013, 71, 109–117.
[3]
Robinson, H.L.; Pertmer, T.M. DNA vaccines for viral infections: Basic studies and applications. Adv. Virus Res. 2000, 55, 1–74.
[4]
Ledgerwood, J.E.; Graham, B.S. DNA vaccines: A safe and efficient platform technology for responding to emerging infectious diseases. Hum. Vaccin. 2009, 5, 623–626.
[5]
Martin, J.E.; Sullivan, N.J.; Enama, M.E.; Gordon, I.J.; Roederer, M.; Koup, R.A.; Bailer, R.T.; Chakrabarti, B.K.; Bailey, M.A.; Gomez, P.L.; et al. A DNA vaccine for Ebola virus is safe and immunogenic in a Phase I clinical trial. Clin. Vaccine Immunol. 2006, 13, 1267–1277, doi:10.1128/CVI.00162-06.
[6]
Martin, J.E.; Pierson, T.C.; Hubka, S.; Rucker, S.; Gordon, I.J.; Enama, M.E.; Andrews, C.A.; Xu, Q.; Davis, B.S.; Nason, M.; et al. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a Phase 1 clinical trial. J. Infect. Dis. 2007, 196, 1732–1740, doi:10.1086/523650.
[7]
Martin, J.E.; Louder, M.K.; Holman, L.A.; Gordon, I.J.; Enama, M.E.; Larkin, B.D.; Andrews, C.A.; Vogel, L.; Koup, R.A.; Roederer, M.; et al. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine 2008, 26, 6338–6343, doi:10.1016/j.vaccine.2008.09.026.
[8]
Ledgerwood, J.E.; Pierson, T.C.; Hubka, S.A.; Desai, N.; Rucker, S.; Gordon, I.J.; Enama, M.E.; Nelson, S.; Nason, M.; Gu, W.; et al. A West Nile virus DNA vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase I clinical trial. J. Infect. Dis. 2011, 203, 1396–1404, doi:10.1093/infdis/jir054.
[9]
Ledgerwood, J.E.; Wei, C.J.; Hu, Z.; Gordon, I.J.; Enama, M.E.; Hendel, C.S.; McTamney, P.M.; Pearce, M.B.; Yassine, H.M.; Boyington, J.C.; et al. DNA priming and influenza vaccine immunogenicity: Two Phase 1 open label randomised clinical trials. Lancet Infect. Dis. 2011, 11, 916–924, doi:10.1016/S1473-3099(11)70240-7.
[10]
Tang, D.C.; DeVit, M.; Johnston, S.A. Genetic immunization is a simple method for eliciting an immune response. Nature 1992, 356, 152–154, doi:10.1038/356152a0.
[11]
Chang, D.C.; Liu, W.J.; Anraku, I.; Clark, D.C.; Pollitt, C.C.; Suhrbier, A.; Hall, R.A.; Khromykh, A.A. Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus. Nat. Biotechnol. 2008, 26, 571–577, doi:10.1038/nbt1400.
Sommerset, I.; Krossoy, B.; Biering, E.; Frost, P. Vaccines for fish in aquaculture. Expert Rev. Vaccines 2005, 4, 89–101, doi:10.1586/14760584.4.1.89.
[14]
Bar-Or, A.; Vollmer, T.; Antel, J.; Arnold, D.L.; Bodner, C.A.; Campagnolo, D.; Gianettoni, J.; Jalili, F.; Kachuck, N.; Lapierre, Y.; et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch. Neurol. 2007, 64, 1407–1415, doi:10.1001/archneur.64.10.nct70002.
[15]
Papadopoulou, A.; von Felten, S.; Traud, S.; Rahman, A.; Quan, J.; King, R.; Garren, H.; Steinman, L.; Cutter, G.; Kappos, L.; et al. Evolution of MS lesions to black holes under DNA vaccine treatment. J. Neurol. 2012, 259, 1375–1382, doi:10.1007/s00415-011-6361-x.
[16]
Lambracht-Washington, D.; Rosenberg, R.N. Active DNA Aβ42 vaccination as immunotherapy for Alzheimer disease. Transl. Neurosci. 2012, 3, 307–313, doi:10.2478/s13380-012-0037-6.
[17]
Jounai, N.; Okuda, K.; Kojima, Y.; Toda, Y.; Hamajima, K.; Ohba, K.; Klinman, D.; Xin, K.Q. Contribution of the rev gene to the immunogenicity of DNA vaccines targeting the envelope glycoprotein of HIV. J. Gene Med. 2003, 5, 609–617, doi:10.1002/jgm.391.
[18]
Shoji, M.; Yoshizaki, S.; Mizuguchi, H.; Okuda, K.; Shimada, M. Immunogenic comparison of chimeric adenovirus 5/35 vector carrying optimized human immunodeficiency virus clade C genes and various promoters. PLoS One 2012, 7, e30302.
[19]
Ulmer, J.B.; Deck, R.R.; DeWitt, C.M.; Friedman, A.; Donnelly, J.J.; Liu, M.A. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. Vaccine 1994, 12, 1541–1544, doi:10.1016/0264-410X(94)90081-7.
[20]
Barry, M.A.; Lai, W.C.; Johnston, S.A. Protection against mycoplasma infection using expression-library immunization. Nature 1995, 377, 632–635, doi:10.1038/377632a0.
[21]
Donnelly, J.J.; Friedman, A.; Martinez, D.; Montgomery, D.L.; Shiver, J.W.; Motzel, S.L.; Ulmer, J.B.; Liu, M.A. Preclinical efficacy of a prototype DNA vaccine: Enhanced protection against antigenic drift in influenza virus. Nat. Med. 1995, 1, 583–587, doi:10.1038/nm0695-583.
[22]
Widera, G.; Austin, M.; Rabussay, D.; Goldbeck, C.; Barnett, S.W.; Chen, M.; Leung, L.; Otten, G.R.; Thudium, K.; Selby, M.J.; et al. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J. Immunol. 2000, 164, 4635–4640.
Feltquate, D.M.; Heaney, S.; Webster, R.G.; Robinson, H.L. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 1997, 158, 2278–2284.
[25]
Boyle, C.M.; Morin, M.; Webster, R.G.; Robinson, H.L. Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein. J. Virol. 1996, 70, 9074–9078.
[26]
Fynan, E.F.; Webster, R.G.; Fuller, D.H.; Haynes, J.R.; Santoro, J.C.; Robinson, H.L. DNA vaccines: Protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. USA 1993, 90, 11478–11482, doi:10.1073/pnas.90.24.11478.
[27]
Tadokoro, K.; Koizumi, Y.; Miyagi, Y.; Kojima, Y.; Kawamoto, S.; Hamajima, K.; Okuda, K.; Tanaka, S.; Onari, K.; Wahren, B.; et al. Rapid and wide-reaching delivery of HIV-1 env DNA vaccine by intranasal administration. Viral Immunol. 2001, 14, 159–167, doi:10.1089/088282401750234538.
[28]
Okada, E.; Sasaki, S.; Ishii, N.; Aoki, I.; Yasuda, T.; Nishioka, K.; Fukushima, J.; Miyazaki, J.; Wahren, B.; Okuda, K. Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J. Immunol. 1997, 159, 3638–3647.
[29]
Asakura, Y.; Hinkula, J.; Leandersson, A.C.; Fukushima, J.; Okuda, K.; Wahren, B. Induction of HIV-1 specific mucosal immune responses by DNA vaccination. Scand. J. Immunol. 1997, 46, 326–330.
[30]
Wang, D.; Christopher, M.E.; Nagata, L.P.; Zabielski, M.A.; Li, H.; Wong, J.P.; Samuel, J. Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza virus hemagglutinin elicits mucosal, cellular and humoral immune responses. J. Clin. Virol. 2004, 31, S99–S106, doi:10.1016/j.jcv.2004.09.013.
[31]
Liu, L.J.; Watabe, S.; Yang, J.; Hamajima, K.; Ishii, N.; Hagiwara, E.; Onari, K.; Xin, K.Q.; Okuda, K. Topical application of HIV DNA vaccine with cytokine-expression plasmids induces strong antigen-specific immune responses. Vaccine 2001, 20, 42–48, doi:10.1016/S0264-410X(01)00324-3.
[32]
Watabe, S.; Xin, K.Q.; Ihata, A.; Liu, L.J.; Honsho, A.; Aoki, I.; Hamajima, K.; Wahren, B.; Okuda, K. Protection against influenza virus challenge by topical application of influenza DNA vaccine. Vaccine 2001, 19, 4434–4444, doi:10.1016/S0264-410X(01)00194-3.
[33]
Daheshia, M.; Kuklin, N.; Kanangat, S.; Manickan, E.; Rouse, B.T. Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10. J. Immunol. 1997, 159, 1945–1452.
[34]
Kask, A.S.; Chen, X.; Marshak, J.O.; Dong, L.; Saracino, M.; Chen, D.; Jarrahian, C.; Kendall, M.A.; Koelle, D.M. DNA vaccine delivery by densely-packed and short microprojection arrays to skin protects against vaginal HSV-2 challenge. Vaccine 2010, 28, 7483–7491, doi:10.1016/j.vaccine.2010.09.014.
[35]
Okuda, K.; Xin, K.Q.; Haruki, A.; Kawamoto, S.; Kojima, Y.; Hirahara, F.; Okada, H.; Klinman, D.; Hamajima, K. Transplacental genetic immunization after intravenous delivery of plasmid DNA to pregnant mice. J. Immunol. 2001, 167, 5478–5484.
[36]
Graham, B.S.; Enama, M.E.; Nason, M.C.; Gordon, I.J.; Peel, S.A.; Ledgerwood, J.E.; Plummer, S.A.; Mascola, J.R.; Bailer, R.T.; Roederer, M.; et al. DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial. PLoS One 2013, 8, e59340, doi:10.1371/journal.pone.0059340.
[37]
Tavel, J.A.; Martin, J.E.; Kelly, G.G.; Enama, M.E.; Shen, J.M.; Gomez, P.L.; Andrews, C.A.; Koup, R.A.; Bailer, R.T.; Stein, J.A.; et al. Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects. J. Acquir. Immune Defic. Syndr. 2007, 44, 601–605, doi:10.1097/QAI.0b013e3180417cb6.
[38]
Sardesai, N.Y.; Weiner, D.B. Electroporation delivery of DNA vaccines: Prospects for success. Curr. Opin. Immunol. 2011, 23, 421–429, doi:10.1016/j.coi.2011.03.008.
[39]
Luxembourg, A.; Hannaman, D.; Ellefsen, B.; Nakamura, G.; Bernard, R. Enhancement of immune responses to an HBV DNA vaccine by electroporation. Vaccine 2006, 24, 4490–4493, doi:10.1016/j.vaccine.2005.08.014.
[40]
Vasan, S.; Hurley, A.; Schlesinger, S.J.; Hannaman, D.; Gardiner, D.F.; Dugin, D.P.; Boente-Carrera, M.; Vittorino, R.; Caskey, M.; Andersen, J.; et al. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One 2011, 6, e19252, doi:10.1371/journal.pone.0019252.
[41]
Luckay, A.; Sidhu, M.K.; Kjeken, R.; Megati, S.; Chong, S.Y.; Roopchand, V.; Garcia-Hand, D.; Abdullah, R.; Braun, R.; Montefiori, D.C.; et al. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in Rhesus macaques. J. Virol. 2007, 81, 5257–5269, doi:10.1128/JVI.00055-07.
[42]
Zhou, J.; Cheung, A.K.; Tan, Z.; Wang, H.; Yu, W.; Du, Y.; Kang, Y.; Lu, X.; Liu, L.; Yuen, K.Y.; et al. PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice. J. Clin. Invest. 2013, 123, 2629–2642, doi:10.1172/JCI64704.
[43]
Donate, A.; Coppola, D.; Cruz, Y.; Heller, R. Evaluation of a novel non-penetrating electrode for use in DNA vaccination. PLoS One 2011, 6, e19181.
Heller, L.C.; Heller, R. Electroporation gene therapy preclinical and clinical trials for melanoma. Curr. Gene Ther. 2010, 10, 312–317, doi:10.2174/156652310791823489.
[46]
Bordbar, B.; Gnidehou, S.; Ndam, N.T.; Doritchamou, J.; Moussiliou, A.; Quiviger, M.; Deloron, P.; Scherman, D.; Bigey, P. Electroporation-mediated genetic vaccination for antigen mapping: application to Plasmodium falciparum VAR2CSA protein. Bioelectrochemistry 2012, 87, 132–137, doi:10.1016/j.bioelechem.2011.12.009.
[47]
Romero, E.L.; Morilla, M.J. Topical and mucosal liposomes for vaccine delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2011, 3, 356–375, doi:10.1002/wnan.131.
[48]
Ishii, N.; Fukushima, J.; Kaneko, T.; Okada, E.; Tani, K.; Tanaka, S.I.; Hamajima, K.; Xin, K.Q.; Kawamoto, S.; Koff, W.; et al. Cationic liposomes are a strong adjuvant for a DNA vaccine of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses 1997, 13, 1421–1428, doi:10.1089/aid.1997.13.1421.
[49]
Xin, K.Q.; Hamajima, K.; Sasaki, S.; Honsho, A.; Tsuji, T.; Ishii, N.; Cao, X.R.; Lu, Y.; Fukushima, J.; Shapshak, P.; et al. Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA vaccine with interleukin-2 expression plasmid enhances cell-mediated immunity against HIV-1. Immunology 1998, 94, 438–444, doi:10.1046/j.1365-2567.1998.00533.x.
[50]
Tsuji, T.; Hamajima, K.; Fukushima, J.; Xin, K.Q.; Ishii, N.; Aoki, I.; Ishigatsubo, Y.; Tani, K.; Kawamoto, S.; Nitta, Y.; et al. Enhancement of cell-mediated immunity against HIV-1 induced by coinnoculation of plasmid-encoded HIV-1 antigen with plasmid expressing IL-12. J. Immunol. 1997, 158, 4008–4013.
[51]
Yi, A.K.; Chace, J.H.; Cowdery, J.S.; Krieg, A.M. IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides. J. Immunol. 1996, 156, 558–564.
[52]
Sasaki, S.; Sumino, K.; Hamajima, K.; Fukushima, J.; Ishii, N.; Kawamoto, S.; Mohri, H.; Kensil, C.R.; Okuda, K. Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes. J. Virol. 1998, 72, 4931–4939.
[53]
Weiss, W.R.; Ishii, K.J.; Hedstrom, R.C.; Sedegah, M.; Ichino, M.; Barnhart, K.; Klinman, D.M.; Hoffman, S.L. A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine. J. Immunol. 1998, 161, 2325–2332.
[54]
Arai, H.; Xin, K.Q.; Hamajima, K.; Lu, Y.; Watabe, S.; Takahashi, T.; Toda, S.; Okuda, K.; Kudoh, I.; Suzuki, M.; et al. 8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine. Gene Ther. 2000, 7, 694–702, doi:10.1038/sj.gt.3301145.
[55]
Krieg, A.M.; Yi, A.K.; Matson, S.; Waldschmidt, T.J.; Bishop, G.A.; Teasdale, R.; Koretzky, G.A.; Klinman, D.M. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995, 374, 546–549, doi:10.1038/374546a0.
[56]
Klinman, D.M.; Yamshchikov, G.; Ishigatsubo, Y. Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 1997, 158, 3635–3639.
[57]
Krieg, A.M.; Wu, T.; Weeratna, R.; Efler, S.M.; Love-Homan, L.; Yang, L.; Yi, A.K.; Short, D.; Davis, H.L. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc. Natl. Acad. Sci. USA 1998, 95, 12631–12636, doi:10.1073/pnas.95.21.12631.
[58]
Vollmer, J.; Krieg, A.M. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv. Drug Deliv. Rev. 2009, 61, 195–204, doi:10.1016/j.addr.2008.12.008.
[59]
Qi, X.F.; Zheng, L.; Kim, C.S.; Lee, K.J.; Kim, D.H.; Cai, D.Q.; Qin, J.W.; Yu, Y.H.; Wu, Z.; Kim, S.K. CpG oligodeoxynucleotide induces apoptosis and cell cycle arrest in A20 lymphoma cells via TLR9-mediated pathways. Mol. Immunol. 2013, 54, 327–337, doi:10.1016/j.molimm.2013.01.001.
[60]
Dar, P.A.; Ganesh, K.; Nagarajan, G.; Sarika, S.; Reddy, G.R.; Suryanarayana, V.V. Sindbis virus replicase-based DNA vaccine construct encoding FMDV-specific multivalent epitope gene: Studies on its immune responses in guinea pigs. Scand. J. Immunol. 2012, 76, 345–353, doi:10.1111/j.1365-3083.2012.02733.x.
Abdulhaqq, S.A.; Weiner, D.B. DNA vaccines: Developing new strategies to enhance immune responses. Immunol. Res. 2008, 42, 219–232, doi:10.1007/s12026-008-8076-3.
[63]
Halbherr, S.J.; Brostoff, T.; Tippenhauer, M.; Locher, S.; Rentsch, M.B.; Zimmer, G. Vaccination with recombinant RNA replicon particles protects chickens from H5N1 highly pathogenic avian influenza virus. PLoS One 2013, 8, e66059.
[64]
Ngai, K.L.; Chan, M.C.; Chan, P.K. Replication and transcription activities of ribonucleoprotein complexes reconstituted from avian H5N1, H1N1pdm09 and H3N2 influenza A viruses. PLoS One 2013, 8, e65038, doi:10.1371/journal.pone.0065038.
Geall, A.J.; Verma, A.; Otten, G.R.; Shaw, C.A.; Hekele, A.; Banerjee, K.; Cu, Y.; Beard, C.W.; Brito, L.A.; Krucker, T.; et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl. Acad. Sci. USA 2012, 109, 14604–14609, doi:10.1073/pnas.1209367109.
[67]
Schwartz, L.; Brown, G.V.; Genton, B.; Moorthy, V.S. A review of malaria vaccine clinical projects based on the WHO rainbow table. Malar. J. 2012, 11, doi:10.1186/1475-2875-11-11.
[68]
Matano, T.; Kobayashi, M.; Igarashi, H.; Takeda, A.; Nakamura, H.; Kano, M.; Sugimoto, C.; Mori, K.; Iida, A.; Hirata, T.; et al. Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. J. Exp. Med. 2004, 199, 1709–1718, doi:10.1084/jem.20040432.
[69]
Sedegah, M.; Jones, T.R.; Kaur, M.; Hedstrom, R.; Hobart, P.; Tine, J.A.; Hoffman, S.L. Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine. Proc. Natl. Acad. Sci. USA 1998, 95, 7648–7653.
[70]
Jiang, G.; Shi, M.; Conteh, S.; Richie, N.; Banania, G.; Geneshan, H.; Valencia, A.; Singh, P.; Aguiar, J.; Limbach, K.; et al. Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: Comparison of heterologous prime boost strategies. PLoS One 2009, 4, e6559, doi:10.1371/journal.pone.0006559.
[71]
Gabitzsch, E.S.; Xu, Y.; Yoshida, L.H.; Balint, J.; Amalfitano, A.; Jones, F.R. Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity. Vaccine 2009, 27, 6394–6398, doi:10.1016/j.vaccine.2009.06.028.
[72]
Xin, K.Q.; Jounai, N.; Someya, K.; Honma, K.; Mizuguchi, H.; Naganawa, S.; Kitamura, K.; Hayakawa, T.; Saha, S.; Takeshita, F.; et al. Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV. Gene Ther. 2005, 12, 1769–1777, doi:10.1038/sj.gt.3302590.
[73]
Chuang, I.; Sedegah, M.; Cicatelli, S.; Spring, M.; Polhemus, M.; Tamminga, C.; Patterson, N.; Guerrero, M.; Bennett, J.W.; McGrath, S.; et al. DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PLoS One 2013, 8, e55571, doi:10.1371/journal.pone.0055571.
[74]
Rogers, W.O.; Baird, J.K.; Kumar, A.; Tine, J.A.; Weiss, W.; Aguiar, J.C.; Gowda, K.; Gwadz, R.; Kumar, S.; Gold, M.; et al. Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques. Infect. Immun. 2001, 69, 5565–5572, doi:10.1128/IAI.69.9.5565-5572.2001.
[75]
Wilks, A.B.; Christian, E.C.; Seaman, M.S.; Sircar, P.; Carville, A.; Gomez, C.E.; Esteban, M.; Pantaleo, G.; Barouch, D.H.; Letvin, N.L.; et al. Robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus DNA prime and live virus vector boost vaccination of lactating rhesus monkeys. J. Immunol. 2010, 185, 7097–7106, doi:10.4049/jimmunol.1002751.
[76]
Fiedler, M.; Kosinska, A.; Schumann, A.; Brovko, O.; Walker, A.; Lu, M.; Johrden, L.; Mayer, A.; Wildner, O.; Roggendorf, M. Prime/Boost immunization with DNA and adenoviral vectors protects from hepatitis D virus (HDV) infection after simultaneous infection with HDV and woodchuck hepatitis virus. J. Virol. 2013, 87, 7708–7716, doi:10.1128/JVI.00645-13.
[77]
Winstone, N.; Wilson, A.J.; Morrow, G.; Boggiano, C.; Chiuchiolo, M.J.; Lopez, M.; Kemelman, M.; Ginsberg, A.A.; Mullen, K.; Coleman, J.W.; et al. Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239 replication in macaques immunized with an interleukin-12 plasmid and a DNA prime-viral vector boost vaccine regimen. J. Virol. 2011, 85, 9578–9587, doi:10.1128/JVI.05060-11.
[78]
O’Connell, R.J.; Kim, J.H.; Corey, L.; Michael, N.L. Human immunodeficiency virus vaccine trials. Cold Spring Harb. Perspect Med. 2012, 2, a007351.
[79]
Weiss, W.R.; Kumar, A.; Jiang, G.; Williams, J.; Bostick, A.; Conteh, S.; Fryauff, D.; Aguiar, J.; Singh, M.; O’Hagan, D.T.; et al. Protection of rhesus monkeys by a DNA prime/poxvirus boost malaria vaccine depends on optimal DNA priming and inclusion of blood stage antigens. PLoS One 2007, 2, e1063, doi:10.1371/journal.pone.0001063.
