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Expert Review of Vaccines Volume 10, 2011 - Issue 11
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Review

Adenovirus-vectored drug–vaccine duo as a potential driver for conferring mass protection against infectious diseases

Jianfeng Zhang Vaxin Inc., 1500 First Avenue North, Birmingham, AL 35203, USA; Vaxin Inc., 1500 First Avenue North, Birmingham, AL 35203, USA
,
E Bart Tarbet Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA; Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA
,
Haroldo Toro Department of Pathobiology, Auburn University, Auburn, AL 36849, USA; Department of Pathobiology, Auburn University, Auburn, AL 36849, USA
&
De-chu C Tang Vaxin Inc., 1500 First Avenue North, Birmingham, AL 35203, USA;[email protected]
Pages 1539-1552 | Published online: 09 Jan 2014

References

  • Salomon ME, Halperin R, Yee J. Evaluation of the two-needle strategy for reducing reactions to DPT vaccination. Am. J. Dis. Child.141, 796–798 (1987).
  • Lanza GA, Barone L, Scalone G et al. Inflammation-related effects of adjuvant influenza A vaccination on platelet activation and cardiac autonomic function. J. Intern. Med.269, 118–125 (2011).
  • Jae SY, Heffernan KS, Park SH et al. Does an acute inflammatory response temporarily attenuate parasympathetic reactivation? Clin. Auton. Res.20, 229–233 (2010).
  • Sever JL, Brenner AI, Gale AD et al. Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiol. Drug Saf.13, 825–840 (2004).
  • Minor P. Vaccine-derived poliovirus (VDPV): impact on poliomyelitis eradication. Vaccine27, 2649–2652 (2009).
  • Poland GA, Grabenstein JD, Neff JM. The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program. Vaccine23, 2078–2081 (2005).
  • Lewis DJ, Huo Z, Barnett S et al. Transient facial nerve paralysis (Bell’s palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin. PLoS ONE4, e6999 (2009).
  • Couch RB. Nasal vaccination, Escherichia coli enterotoxin, and Bell’s palsy. N. Engl. J. Med.350, 860–861 (2004).
  • Carlson BC, Jansson AM, Larsson A, Bucht A, Lorentzen JC. The endogenous adjuvant squalene can induce a chronic T-cell-mediated arthritis in rats. Am. J. Pathol.156, 2057–2065 (2000).
  • Finch CE, Crimmins EM. Inflammatory exposure and historical changes in human life-spans. Science305, 1736–1739 (2004).
  • Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu. Rev. Immunol.29, 415–445 (2011).
  • O’Callaghan DS, O’Donnell D, O’Connell F, O’Byrne KJ. The role of inflammation in the pathogenesis of non-small cell lung cancer. J. Thorac. Oncol.5, 2024–2036 (2010).
  • Witte ME, Geurts JJ, de Vries HE, van der Valk P, van Horssen J. Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion10, 411–418 (2010).
  • Gallichan WS, Rosenthal KL. Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization. J. Exp. Med.184, 1879–1890 (1996).
  • Saurer L, McCullough KC, Summerfield A. In vitro induction of mucosa-type dendritic cells by all-trans retinoic acid. J. Immunol.179, 3504–3514 (2007).
  • Molenaar R, Greuter M, van der Marel AP et al. Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J. Immunol.183, 6395–6402 (2009).
  • Tang DC, Van Kampen KR. Toward the development of vectored vaccines in compliance with evolutionary medicine. Expert Rev. Vaccines7(4), 399–402 (2008).
  • Karron RA, Talaat K, Luke C et al. Evaluation of two live attenuated cold-adapted H5N1 influenza virus vaccines in healthy adults. Vaccine27, 4953–4960 (2009).
  • Van Kampen KR, Shi Z, Gao P et al. Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans. Vaccine23, 1029–1036 (2005).
  • Tang DC, Shi Z, Curiel DT. Vaccination onto bare skin. Nature388, 729–730 (1997).
  • Zhang J, Shi Z, Kong FK et al. Topical application of Escherichia coli-vectored vaccine as a simple method for eliciting protective immunity. Infect. Immun.74, 3607–3617 (2006).
  • Glenn GM, Taylor DN, Li X et al. Transcutaneous immunization: a human vaccine delivery strategy using a patch. Nat. Med.6, 1403–1406 (2000).
  • Sullivan SP, Koutsonanos DG, del Pilar Martin M et al. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med.16, 915–920 (2010).
  • Kaplan DH. In vivo function of Langerhans cells and dermal dendritic cells. Trends Immunol.31, 446–451 (2010).
  • Soloff AC, Barratt-Boyes SM. Enemy at the gates: dendritic cells and immunity to mucosal pathogens. Cell Res.20, 872–885 (2010).
  • Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human gammadelta T cells. Science309, 264–268 (2005).
  • Feng T, Cong Y, Qin H, Benveniste EN, Elson CO. Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. J. Immunol.185, 5915–5925 (2010).
  • Kaufman DR, Bivas-Benita M, Simmons NL, Miller D, Barouch DH. Route of adenovirus-based HIV-1 vaccine delivery impacts the phenotype and trafficking of vaccine-elicited CD8+ T lymphocytes. J. Virol.84, 5986–5996 (2010).
  • San Martín C, Burnett RM. Structural studies on adenoviruses. Curr. Top. Microbiol. Immunol.272, 57–94 (2003).
  • Lichtenstein DL, Wold WS. Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission. Cancer Gene Ther.11, 819–829 (2004).
  • Howell MR, Nang RN, Gaydos CA, Gaydos JC. Prevention of adenoviral acute respiratory disease in Army recruits: cost–effectiveness of a military vaccination policy. Am. J. Prev. Med.14, 168–175 (1998).
  • Haj-Ahmad Y, Graham FL. Development of a helper-independent human adenovirus vector and its use in the transfer of the herpes simplex virus thymidine kinase gene. J. Virol.57, 267–274 (1986).
  • Zhu J, Grace M, Casale J et al. Characterization of replication-competent adenovirus isolates from large-scale production of a recombinant adenoviral vector. Hum. Gene Ther.10, 113–121 (1999).
  • Fallaux FJ, Bout A, van der Velde I et al. New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum. Gene Ther.9, 1909–1917 (1998).
  • Tang DC, Zhang J, Toro H, Shi Z, Van Kampen KR. Adenovirus as a carrier for the development of influenza virus-free avian influenza vaccines. Expert Rev. Vaccines8, 469–481 (2009).
  • Wang L, Cheng C, Ko SY et al. Delivery of human immunodeficiency virus vaccine vectors to the intestine induces enhanced mucosal cellular immunity. J. Virol.83, 7166–7175 (2009).
  • Tang J, Olive M, Champagne K et al. Adenovirus hexon T-cell epitope is recognized by most adults and is restricted by HLA DP4, the most common class II allele. Gene Ther.11, 1408–1415 (2004).
  • 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, 351–357 (2004).
  • Barouch DH, Kik SV, Weverling GJ et al. International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine29, 5203–5209 (2011).
  • Yang Y, Nunes FA, Berencsi K et al. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl Acad. Sci. USA91, 4407–4411 (1994).
  • Croyle MA, Patel A, Tran KN et al. Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. PLoS ONE3, e3548 (2008).
  • Stone D, Liu Y, Li ZY et al. Comparison of adenoviruses from species B, C, E, and F after intravenous delivery. Mol. Ther.15, 2146–2153 (2007).
  • Sharma A, Bangari DS, Tandon M et al. Comparative analysis of vector biodistribution, persistence and gene expression following intravenous delivery of bovine, porcine and human adenoviral vectors in a mouse model. Virology386, 44–54 (2009).
  • Roy S, Medina-Jaszek A, Wilson MJ et al. Creation of a panel of vectors based on ape adenovirus isolates. J. Gene Med.13, 17–25 (2011).
  • Patel A, Tikoo S, Kobinger G. A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model. PLoS ONE5, e15301 (2010).
  • Chen EC, Yagi S, Kelly KR et al. Cross-species transmission of a novel adenovirus associated with a fulminant pneumonia outbreak in a new world monkey colony. PLoS Pathog.7, e1002155 (2011).
  • Seto J, Walsh MP, Metzgar D, Seto D. Computational analysis of adenovirus serotype 5 (HAdV-C5) from an HAdV coinfection shows genome stability after 45 years of circulation. Virology404, 180–186 (2010).
  • Boyer JL, Sofer-Podesta C, Ang J et al. Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid. Hum. Gene Ther.21, 891–901 (2010).
  • Worgall S, Krause A, Qiu J et al. Protective immunity to Pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF. J. Virol.81, 13801–13808 (2007).
  • Osada T, Yang XY, Hartman ZC et al. Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity. Cancer Gene Ther.16, 673–682 (2009).
  • Gabitzsch ES, Xu Y, Yoshida LH et al. Novel adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity. Vaccine27, 6394–6398 (2009).
  • Parks RJ, Chen L, Anton M et al. A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc. Natl Acad. Sci. USA93, 13565–13570 (1996).
  • Shi Z, Zeng M, Yang G et al. Protection against tetanus by needle-free inoculation of adenovirus-vectored nasal and epicutaneous vaccines. J. Virol.75, 11474–11482 (2001).
  • Song K, Bolton DL, Wilson RL et al. Genetic immunization in the lung induces potent local and systemic immune responses. Proc. Natl Acad. Sci. USA107, 22213–22218 (2010).
  • Raper SE, Chirmule N, Lee FS et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab.80, 148–158 (2003).
  • Hartman ZC, Appledorn DM, Amalfitano A. Adenovirus vector induced innate immune responses: impact upon efficacy and toxicity in gene therapy and vaccine applications. Virus Res.132, 1–14 (2008).
  • Higashimoto Y, Yamagata Y, Itoh H. Complex effect of adenovirus early region proteins on innate immune system. Inflamm. Allergy Drug Targets5, 229–237 (2006).
  • Buchbinder SP, Mehrotra DV, Duerr A et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet372, 1881–1893 (2008).
  • McElrath MJ, De Rosa SC, Moodie Z et al. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case–cohort analysis. Lancet372, 1894–1905 (2008).
  • Appledorn DM, Aldhamen YA, Godbehere S, Seregin SS, Amalfitano A. Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine confirms Toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity. Clin. Vaccine Immunol.18, 150–160 (2011).
  • Benlahrech A, Harris J, Meiser A et al. Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc. Natl Acad. Sci. USA106, 19940–19945 (2009).
  • Joseph A, Itskovitz-Cooper N, Samira S et al. A new intranasal influenza vaccine based on a novel polycationic lipid – ceramide carbamoyl-spermine (CCS) I. Immunogenicity and efficacy studies in mice. Vaccine24, 3990–4006 (2006).
  • Wang J, Thorson L, Stokes RW et al. Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J. Immunol.173, 6357–6365 (2004).
  • Ockenhouse C. Prime boost regimens of DNA and adenovirus-vectored malaria vaccines: lessons learned from preclinical and clinical studies. Presented at: Conference of Gene Based Vaccines. Vienna, Austria, 13–14 September 2010.
  • McWilliam AS, Nelson DJ, Holt PG. The biology of airway dendritic cells. Immunol. Cell Biol.73, 405–413 (1995).
  • Brandtzaeg P. Potential of nasopharynx-associated lymphoid tissue for vaccine responses in the airways. Am. J. Respir. Crit. Care Med.183, 1595–1604 (2011).
  • Lubeck MD, Natuk RJ, Chengalvala M et al. Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration. AIDS Res. Hum. Retroviruses10, 1443–1449 (1994).
  • Lemiale F, Kong WP, Akyurek LM et al. Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system. J. Virol.77, 10078–10087 (2003).
  • Gallichan WS, Rosenthal KL. Long-term immunity and protection against herpes simplex virus type 2 in the murine female genital tract after mucosal but not systemic immunization. J. Infect. Dis.177, 1155–1161 (1998).
  • Lobanova LM, Baig TT, Tikoo SK, Zakhartchouk AN. Mucosal adenovirus-vectored vaccine for measles. Vaccine28, 7613–7619 (2010).
  • del Rio ML, Bernhardt G, Rodriguez-Barbosa JI, Förster R. Development and functional specialization of CD103+ dendritic cells. Immunol. Rev.234, 268–281 (2010).
  • Zhang Z, Krimmel J, Zhang Z, Hu Z, Seth P. Systemic delivery of a novel liver-detargeted oncolytic adenovirus causes reduced liver toxicity but maintains the antitumor response in a breast cancer bone metastasis model. Hum. Gene Ther. (In Press) (2011).
  • Li C, Ziegler RJ, Cherry M et al. Adenovirus-transduced lung as a portal for delivering alpha-galactosidase A into systemic circulation for Fabry disease. Mol. Ther.5, 745–754 (2002).
  • Toovey S. Influenza-associated central nervous system dysfunction: a literature review. Travel Med. Infect. Dis.6, 114–124 (2008).
  • Carter NJ, Curran MP. Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults. Drugs71, 1591–1622 (2011).
  • Zhang SY, Jouanguy E, Ugolini S et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science317, 1522–1527 (2007).
  • Hoelscher MA, Garg S, Bangari DS et al. Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet367, 475–481 (2006).
  • Gao W, Soloff AC, Lu X et al. Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J. Virol.80, 1959–1964 (2006).
  • Xiang ZQ, Yang Y, Wilson JM, Ertl HC. A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. Virology219, 220–227 (1996).
  • Tang DC, DeVit M, Johnston SA. Genetic immunization is a simple method for eliciting an immune response. Nature356, 152–154 (1992).
  • Jones S, Evans K, McElwaine-Johnn H et al. DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled Phase 1b clinical trial. Vaccine27, 2506–2512 (2009).
  • Ulmer JB, Donnelly JJ, Parker SE et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science259, 1745–1748 (1993).
  • van Drunen Littel-van den Hurk S, Hannaman D. Electroporation for DNA immunization: clinical application. Expert Rev. Vaccines9(5), 503–517 (2010).
  • Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat. Rev. Genet.9, 776–788 (2008).
  • Peng Z. Current status of gendicine in China: recombinant human Ad–p53 agent for treatment of cancers. Hum. Gene Ther.16, 1016–1027 (2005).
  • Evans RK, Nawrocki DK, Isopi LA et al. Development of stable liquid formulations for adenovirus-based vaccines. J. Pharm. Sci.93, 2458–2475 (2004).
  • 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, 19ra12 (2010).
  • Croyle MA, Cheng X, Wilson JM. Development of formulations that enhance physical stability of viral vectors for gene therapy. Gene Ther.8, 1281–1290 (2001).
  • Zhang J, Tarbet EB, Feng T et al. Adenovirus-vectored drug–vaccine duo as a rapid-response tool for conferring seamless protection against influenza. PLoS ONE6, e22605 (2011).
  • Yamaguchi T, Kawabata K, Kouyama E et al. Induction of type I interferon by adenovirus-encoded small RNAs. Proc. Natl Acad. Sci. USA107, 17286–17291 (2010).
  • Thiele AT, Sumpter TL, Walker JA et al. Pulmonary immunity to viral infection: adenovirus infection of lung dendritic cells renders T cells nonresponsive to interleukin-2. J. Virol.80, 1826–1836 (2006).
  • Zhu J, Huang X, Yang Y. A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Mol. Ther.16, 1300–1307 (2008).
  • Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE. Augmented lung inflammation protects against influenza A pneumonia. PLoS ONE4, e4176 (2009).
  • Norton EB, Clements JD, Voss TG, Cárdenas-Freytag L. Prophylactic administration of bacterially derived immunomodulators improves the outcome of influenza virus infection in a murine model. J. Virol.84, 2983–2995 (2010).
  • Poland GA, Jacobson RM, Ovsyannikova IG. Influenza virus resistance to antiviral agents: a plea for rational use. Clin. Infect. Dis.48, 1254–1256 (2009).
  • Takahashi E, Kataoka K, Fujii K et al. Attenuation of inducible respiratory immune responses by oseltamivir treatment in mice infected with influenza A virus. Microbes Infect.12, 778–783 (2010).
  • Toro H, Tang DC, Suarez DL et al. Protective avian influenza in ovo vaccination with non-replicating human adenovirus vector. Vaccine25, 2886–2891 (2007).
  • Toro H, Tang DC, Suarez DL, Zhang J, Shi Z. Protection of chickens against avian influenza with non-replicating adenovirus-vectored vaccine. Vaccine26, 2640–2646 (2008).
  • Toro H, Tang DC. Protection of chickens against avian influenza with nonreplicating adenovirus-vectored vaccine. Poult. Sci.88, 867–871 (2009).
  • Avakian AP, Poston RM, Kong FK, Van Kampen KR, Tang DC. Automated mass immunization of poultry: the prospect for nonreplicating human adenovirus-vectored in ovo vaccines. Expert Rev. Vaccines6(3), 457–465 (2007).
  • Singh S, Toro H, Tang DC et al. Non-replicating adenovirus vectors expressing avian influenza virus hemagglutinin and nucleocapsid proteins induce chicken specific effector, memory and effector memory CD8+ T lymphocytes. Virology405, 62–69 (2010).
  • Toro H, Suarez DL, Tang DC, van Ginkel FW, Breedlovea C. Avian influenza mucosal vaccination in chickens with replication-defective recombinant adenovirus vaccine. Avian Dis.55, 43–47 (2011).
  • van Ginkel F, Tang DC, Gulley SL, Toro H. Induction of mucosal immunity in the avian Harderian gland with a replication-deficient Ad5 vector expressing avian influenza H5 hemagglutinin. Dev. Comp. Immunol.33, 28–34 (2009).
  • Wesley RD, Tang M, Lager KM. Protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of H3N2 swine influenza virus. Vaccine22, 3427–3434 (2004).
  • Toro H, van Ginkel FW, Tang DC et al. Avian influenza vaccination in chickens and pigs with replication-competent adenovirus-free human recombinant adenovirus 5. Avian Dis.54(1 Suppl.), 224–231 (2010).
  • Henderson H, Jackson F, Bean K et al. Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine. Vaccine27, 7194–7197 (2009).
  • 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, 4222–4233 (2011).
  • Pratt WD, Wang D, Nichols DK et al. Protection of nonhuman primates against two species of Ebola virus infection with a single complex adenovirus vector. Clin. Vaccine Immunol.17, 572–581 (2010).
  • Geisbert TW, Bailey M, Geisbert JB et al. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J. Virol.84, 10386–10394 (2010).
  • Xing Z, McFarland CT, Sallenave JM et al. Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis. PLoS ONE4, e5856 (2009).
  • McConnell MJ, Hanna PC, Imperiale MJ. Adenovirus-based prime-boost immunization for rapid vaccination against anthrax. Mol. Ther.15, 203–210 (2007).
  • Wei CJ, Boyington JC, McTamney PM et al. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science329, 1060–1064 (2010).
  • Safronetz D, Hegde NR, Ebihara H et al. Adenovirus vectors expressing hantavirus proteins protect hamsters against lethal challenge with andes virus. J. Virol.83, 7285–7295 (2009).
  • Xu Q, Pichichero ME, Simpson LL et al. An adenoviral vector-based mucosal vaccine is effective in protection against botulism. Gene Ther.16, 367–375 (2009).
  • Chiuchiolo MJ, Boyer JL, Krause A et al. Protective immunity against respiratory tract challenge with Yersinia pestis in mice immunized with an adenovirus-based vaccine vector expressing V antigen. J. Infect. Dis.194, 1249–1257 (2006).
  • Fox JL. FDA, producers moving toward mammalian cell-based flu vaccines. Microbe1, 54–55 (2006).
  • Boyer JL, Kobinger G, Wilson JM, Crystal RG. Adenovirus-based genetic vaccines for biodefense. Hum. Gene Ther.16, 157–168 (2005).

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