2011, 8(1): 77-93. doi: 10.3934/mbe.2011.8.77

The impact of vaccines and vaccinations: Challenges and opportunities for modelers

1. 

Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85281, United States

Received  September 2010 Revised  September 2010 Published  January 2011

This review focuses on how infectious diseases and their prevention and control by development of vaccines and widespread vaccination has shaped evolution of human civilization and of the animals and plants that humans depend on for food, labor and companionship. After describing major infectious diseases and the current status for control by vaccination, the barriers to infection and the attributes of innate and acquired immunity contributing to control are discussed. The evolution in types of vaccines is presented in the context of developing technologies and in improving adjuvants to engender enhanced vaccine efficacy. The special concerns and needs in vaccine design and development are discussed in dealing with epidemics/pandemics with special emphasis on influenza and current global problems in vaccine delivery.
Citation: Roy Curtiss III. The impact of vaccines and vaccinations: Challenges and opportunities for modelers. Mathematical Biosciences & Engineering, 2011, 8 (1) : 77-93. doi: 10.3934/mbe.2011.8.77
References:
[1]

S. Akira, S. Uematsu and O. Takeuchi, Pathogen recognition and innate immunity,, Cell, 124 (2006), 783.

[2]

P. Ansstasiou-Fotaki, E. Deligeoroglou and G. Kreatsas, The GARDASIL vaccine can prevent cervical carcinoma caused by human papilloma virus (HPV) (results from our participation and from the study carried out in Greece),, Akush Ginekol (Sofiia), 46 (2007), 17.

[3]

G. J. Atkins, M. N. Fleeton and B. J. Sheahan, Therapeutic and prophylactic applications of alphavirus vectors,, Expert Rev. Mol. Med., 10 (2008). doi: 10.1017/S1462399408000859.

[4]

O. T. Avery and W. F. Goebel, Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar-protein antigens,, J. Exp. Med., 50 (1929), 533. doi: 10.1084/jem.50.4.533.

[5]

R. Barrett, C. W. Kuzawa, T. McDade and G. J. Armelagos, Emerging and re-emerging infectious diseases: The third epidemiologic transition,, Annu. Rev. Anthropol., 27 (1998), 247. doi: 10.1146/annurev.anthro.27.1.247.

[6]

C. Barrios, P. Brawand, M. Berney, C. Brandt, P. H. Lambert and C. A. Siegrist, Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: Predominance of a Th2-biased pattern which persists after adult boosting,, Eur. J. Immunol., 26 (1996), 1489. doi: 10.1002/eji.1830260713.

[7]

J. M. Barry, "The Great Influenza: The Story of the Deadliest Pandemic in History,", revised ed. Penguin Books, (2004).

[8]

J. G. Bartlett, Planning for avian influenza,, Ann. Intern. Med., 145 (2006), 141.

[9]

G. M. Beards and D. W. Brown, The antigenic diversity of rotaviruses: Significance to epidemiology and vaccine strategies,, Eur. J. Epidemiol., 4 (1988), 1. doi: 10.1007/BF00152685.

[10]

A. S. Beare and R. G. Webster, Replication of avian influenza viruses in humans,, Arch. Virol., 119 (1991), 37. doi: 10.1007/BF01314321.

[11]

M. Beauregard and M. A. Hefford, Enhancement of essential amino acid contents in crops by genetic engineering and protein design,, Plant Biotechnol. J., 4 (2006), 561.

[12]

M. W. Beijerinck, A Contagium vivum fluidum as the cause of the mosaic disease of tobacco leaves,, Centralblatt fur Bacteriologie und Parasitenkunde, 5 (1899), 27.

[13]

E. A. Belongia, S. A. Irving, S. C. Waring, L. A. Coleman, J. K. Meece, M. Vandermause, S. Lindstrom, D. Kempf and D. K. Shay, Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008-2009 (H1N1) and 2007-2008 (H3N2) infections,, JAMA, 304 (2010), 1091.

[14]

R. B. Belshe, Current status of live attenuated influenza virus vaccine in the US,, Virus Res., 103 (2004), 177. doi: 10.1016/j.virusres.2004.02.031.

[15]

R. B. Belshe, P. M. Mendelman, J. Treanor, J. King, W. C. Gruber, P. Piedra, D. I. Bernstein, F. G. Hayden, K. Kotloff, K. Zangwill, D. Iacuzio and M. Wolff, The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children,, N. Engl. J. Med., 338 (1998), 1405. doi: 10.1056/NEJM199805143382002.

[16]

R. B. Belshe, K. L. Nichol, S. B. Black, H. Shinefield, J. Cordova, R. Walker, C. Hessel, I. Cho and P. M. Mendelman, Safety, efficacy, and effectiveness of live, attenuated, cold-adapted influenza vaccine in an indicated population aged 5-49 years,, Clin. Infect Dis., 39 (2004), 920. doi: 10.1086/423001.

[17]

D. R. Bentley and G. G. Brownlee, Sequence of the N2 neuraminidase from influenza virus A/NT/60/68,, Nucleic Acids Res., 10 (1982), 5033. doi: 10.1093/nar/10.16.5033.

[18]

O. G. Berlin, S. M. Novak, R. K. Porschen, E. G. Long, G. N. Stelma and F. W. Schaeffer, Recovery of Cyclospora organisms from patients with prolonged diarrhea,, Clin. Infect Dis., 18 (1994), 606.

[19]

P. L. Bhalla, Genetic engineering of wheat-current challenges and opportunities,, Trends Biotechnol., 24 (2006), 305. doi: 10.1016/j.tibtech.2006.04.008.

[20]

M. E. Bianchi, DAMPs, PAMPs and alarmins: all we need to know about danger,, J. Leukoc Biol., 81 (2007), 1. doi: 10.1189/jlb.0306164.

[21]

O. O. Bilukha and N. Rosenstein, Prevention and control of meningococcal disease,, Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep., 54 (2005), 1.

[22]

R. Bock, Plastid biotechnology: prospects for herbicide and insect resistance, metabolic engineering and molecular farming,, Curr. Opin. Biotechnol, 18 (2007), 100. doi: 10.1016/j.copbio.2006.12.001.

[23]

B. Bottazzi, A. Doni, C. Garlanda and A. Mantovani, An integrated view of humoral innate immunity: Pentraxins as a paradigm,, Annu. Rev. Immunol., 28 (2010), 157. doi: 10.1146/annurev-immunol-030409-101305.

[24]

D. J. Brayden, M. A. Jepson and A. W. Baird, Keynote review: Intestinal Peyer's patch M cells and oral vaccine targeting,, Drug Discov. Today, 10 (2005), 1145. doi: 10.1016/S1359-6446(05)03536-1.

[25]

S. Brighenti and J. Andersson, Induction and regulation of CD8+ cytolytic T cells in human tuberculosis and HIV infection,, Biochem. Biophys Res. Commun., 396 (2010), 50. doi: 10.1016/j.bbrc.2010.02.141.

[26]

I. H. Brown, D. J. Alexander, P. Chakraverty, P. A. Harris and R. J. Manvell, Isolation of an influenza A virus of unusual subtype (H1N7) from pigs in England, and the subsequent experimental transmission from pig to pig,, Vet. Microbiol., 39 (1994), 125. doi: 10.1016/0378-1135(94)90093-0.

[27]

I. H. Brown, P. A. Harris, J. W. McCauley and D. J. Alexander, Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype,, J. Gen. Virol., 79 (Pt 12) (1998), 2947.

[28]

A. Calmette, Preventive vaccination against tuberculosis with BCG,, Proc. R. Soc. Med., 24 (1931), 1481.

[29]

L. A. Campbell, C. C. Kuo and J. T. Grayston, Chlamydia pneumoniae and cardiovascular disease,, Emerg. Infect Dis., 4 (1998), 571. doi: 10.3201/eid0404.980407.

[30]

M. A. Campbell, H. A. Fitzgerald and P. C. Ronald, Engineering pathogen resistance in crop plants,, Transgenic Res., 11 (2002), 599. doi: 10.1023/A:1021109509953.

[31]

M. R. Castrucci, I. Donatelli, L. Sidoli, G. Barigazzi, Y. Kawaoka and R. G. Webster, Genetic reassortment between avian and human influenza A viruses in Italian pigs,, Virology, 193 (1993), 503. doi: 10.1006/viro.1993.1155.

[32]

T. M. Chambers, V. S. Hinshaw, Y. Kawaoka, B. C. Easterday and R. G. Webster, Influenza viral infection of swine in the United States 1988-1989,, Arch. Virol., 116 (1991), 261. doi: 10.1007/BF01319247.

[33]

Z. Chen, A. Aspelund, G. Kemble and H. Jin, Genetic mapping of the cold-adapted phenotype of B/Ann Arbor/1/66, the master donor virus for live attenuated influenza vaccines (FluMist),, Virology, 345 (2006), 416. doi: 10.1016/j.virol.2005.10.005.

[34]

K. M. Citron, BCG vaccination against tuberculosis: International perspectives,, Bmj, 306 (1993), 222.

[35]

H. F. Clark, P. A. Offit, R. W. Ellis, J. J. Eiden, D. Krah, A. R. Shaw, M. Pichichero, J. J. Treanor, F. E. Borian, L. M. Bell and S. A. Plotkin, The development of multivalent bovine rotavirus (strain WC3) reassortant vaccine for infants,, J. Infect Dis., 174 Suppl 1S (1996), 73.

[36]

J. Cohen and M. Enserink, Swine flu. after delays, WHO agrees: The 2009 pandemic has begun,, Science, 324 (2009), 1496. doi: 10.1126/science.324_1496.

[37]

G. A. Colditz, C. S. Berkey, F. Mosteller, T. F. Brewer, M. E. Wilson, E. Burdick and H. V. Fineberg, The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: Meta-analyses of the published literature,, Pediatrics, 96 (1995), 29.

[38]

D. B. Collinge, H. J. Jorgensen, O. S. Lund and M. F. Lyngkjaer, Engineering pathogen resistance in crop plants: Current trends and future prospects,, Annu. Rev. Phytopathol., 48 (2010), 269. doi: 10.1146/annurev-phyto-073009-114430.

[39]

G. Corradin and G. del Giudice, "Novel Adjuvants for Vaccines,", Current Medicinal Chemistry Anti-inflammatory and anti-allergy agents 4, (2005).

[40]

R. Curtiss, 3rd, W. Xin, Y. Li, W. Kong, S. Y. Wanda, B. Gunn and S. Wang, New technologies in using recombinant attenuated Salmonella vaccine vectors,, Crit. Rev. Immunol., 30 (2010), 255.

[41]

G. De Becker, V. Moulin, B. Pajak, C. Bruck, M. Francotte, C. Thiriart, J. Urbain and M. Moser, The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells,, Int. Immunol., 12 (2000), 807. doi: 10.1093/intimm/12.6.807.

[42]

P. Delves, S. Martin, D. Burton and I. Roitt, "Essential Immunology,", 11th ed. Wiley-Blackwell, (2006).

[43]

J. Diamond, "Guns, Gems and Steel: The Fates of Human Societies,", 1st ed., (1997).

[44]

R. Dommett, M. Zilbauer, J. T. George and M. Bajaj-Elliott, Innate immune defence in the human gastrointestinal tract,, Mol. Immunol., 42 (2005), 903. doi: 10.1016/j.molimm.2004.12.004.

[45]

M. L. Duran-Reynals, "The Fever Bark Tree: The Pageant of Quinine,", Doubleday, (1946).

[46]

J. L. Ebersole, M. A. Taubman, D. J. Smith and J. M. Goodson, Gingival crevicular fluid antibody to oral microorganisms. I. Method of collection and analysis of antibody,, J. Periodontal Res., 19 (1984), 124. doi: 10.1111/j.1600-0765.1984.tb00801.x.

[47]

P. Ehrlich, Ueber moderne Chemotherapie. Vortrag gehalten in der X,, Tagung der Deutschen Dermatologischen Gesellschaft. Akademische Verlagsgesellschaft m.b.H., (1908).

[48]

T. C. Elleman, A. A. Azad and C. W. Ward, Neuraminidase gene from the early Asian strain of human influenza virus, A/RI/5-/57 (H2N2),, Nucleic Acids Res., 10 (1982), 7005. doi: 10.1093/nar/10.21.7005.

[49]

L. Epstein and S. Bassein, Patterns of pesticide use in California and the implications for strategies for reduction of pesticides,, Annu. Rev. Phytopathol., 41 (2003), 351. doi: 10.1146/annurev.phyto.41.052002.095612.

[50]

N. Ferry, M. G. Edwards, J. A. Gatehouse and A. M. Gatehouse, Plant-insect interactions: molecular approaches to insect resistance,, Curr. Opin. Biotechnol., 15 (2004), 155. doi: 10.1016/j.copbio.2004.01.008.

[51]

R. H. Ffrench-Constant, P. J. Daborn and G. Le Goff, The genetics and genomics of insecticide resistance,, Trends Genet., 20 (2004), 163. doi: 10.1016/j.tig.2004.01.003.

[52]

A. Fleming, On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenza,, Brit. J. Exp. Path., 10 (1929), 226.

[53]

J. E. Galen and M. M. Levine, Can a 'flawless' live vector vaccine strain be engineered?, Trends Microbiol., 9 (2001), 372. doi: 10.1016/S0966-842X(01)02096-0.

[54]

L. Garrett, "The Coming Plague: Newly Emerging Diseases in a World Out of Balance,", 1st ed. Penguin, (1995).

[55]

R. J. Garten, C. T. Davis, C. A. Russell, B. Shu, S. Lindstrom, A. Balish, W. M. Sessions, X. Xu, E. Skepner, V. Deyde, M. Okomo-Adhiambo, L. Gubareva, J. Barnes, C. B. Smith, S. L. Emery, M. J. Hillman, P. Rivailler, J. Smagala, M. de Graaf, D. F. Burke, Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans,, Science, 325 (2009), 197.

show all references

References:
[1]

S. Akira, S. Uematsu and O. Takeuchi, Pathogen recognition and innate immunity,, Cell, 124 (2006), 783.

[2]

P. Ansstasiou-Fotaki, E. Deligeoroglou and G. Kreatsas, The GARDASIL vaccine can prevent cervical carcinoma caused by human papilloma virus (HPV) (results from our participation and from the study carried out in Greece),, Akush Ginekol (Sofiia), 46 (2007), 17.

[3]

G. J. Atkins, M. N. Fleeton and B. J. Sheahan, Therapeutic and prophylactic applications of alphavirus vectors,, Expert Rev. Mol. Med., 10 (2008). doi: 10.1017/S1462399408000859.

[4]

O. T. Avery and W. F. Goebel, Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar-protein antigens,, J. Exp. Med., 50 (1929), 533. doi: 10.1084/jem.50.4.533.

[5]

R. Barrett, C. W. Kuzawa, T. McDade and G. J. Armelagos, Emerging and re-emerging infectious diseases: The third epidemiologic transition,, Annu. Rev. Anthropol., 27 (1998), 247. doi: 10.1146/annurev.anthro.27.1.247.

[6]

C. Barrios, P. Brawand, M. Berney, C. Brandt, P. H. Lambert and C. A. Siegrist, Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: Predominance of a Th2-biased pattern which persists after adult boosting,, Eur. J. Immunol., 26 (1996), 1489. doi: 10.1002/eji.1830260713.

[7]

J. M. Barry, "The Great Influenza: The Story of the Deadliest Pandemic in History,", revised ed. Penguin Books, (2004).

[8]

J. G. Bartlett, Planning for avian influenza,, Ann. Intern. Med., 145 (2006), 141.

[9]

G. M. Beards and D. W. Brown, The antigenic diversity of rotaviruses: Significance to epidemiology and vaccine strategies,, Eur. J. Epidemiol., 4 (1988), 1. doi: 10.1007/BF00152685.

[10]

A. S. Beare and R. G. Webster, Replication of avian influenza viruses in humans,, Arch. Virol., 119 (1991), 37. doi: 10.1007/BF01314321.

[11]

M. Beauregard and M. A. Hefford, Enhancement of essential amino acid contents in crops by genetic engineering and protein design,, Plant Biotechnol. J., 4 (2006), 561.

[12]

M. W. Beijerinck, A Contagium vivum fluidum as the cause of the mosaic disease of tobacco leaves,, Centralblatt fur Bacteriologie und Parasitenkunde, 5 (1899), 27.

[13]

E. A. Belongia, S. A. Irving, S. C. Waring, L. A. Coleman, J. K. Meece, M. Vandermause, S. Lindstrom, D. Kempf and D. K. Shay, Clinical characteristics and 30-day outcomes for influenza A 2009 (H1N1), 2008-2009 (H1N1) and 2007-2008 (H3N2) infections,, JAMA, 304 (2010), 1091.

[14]

R. B. Belshe, Current status of live attenuated influenza virus vaccine in the US,, Virus Res., 103 (2004), 177. doi: 10.1016/j.virusres.2004.02.031.

[15]

R. B. Belshe, P. M. Mendelman, J. Treanor, J. King, W. C. Gruber, P. Piedra, D. I. Bernstein, F. G. Hayden, K. Kotloff, K. Zangwill, D. Iacuzio and M. Wolff, The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children,, N. Engl. J. Med., 338 (1998), 1405. doi: 10.1056/NEJM199805143382002.

[16]

R. B. Belshe, K. L. Nichol, S. B. Black, H. Shinefield, J. Cordova, R. Walker, C. Hessel, I. Cho and P. M. Mendelman, Safety, efficacy, and effectiveness of live, attenuated, cold-adapted influenza vaccine in an indicated population aged 5-49 years,, Clin. Infect Dis., 39 (2004), 920. doi: 10.1086/423001.

[17]

D. R. Bentley and G. G. Brownlee, Sequence of the N2 neuraminidase from influenza virus A/NT/60/68,, Nucleic Acids Res., 10 (1982), 5033. doi: 10.1093/nar/10.16.5033.

[18]

O. G. Berlin, S. M. Novak, R. K. Porschen, E. G. Long, G. N. Stelma and F. W. Schaeffer, Recovery of Cyclospora organisms from patients with prolonged diarrhea,, Clin. Infect Dis., 18 (1994), 606.

[19]

P. L. Bhalla, Genetic engineering of wheat-current challenges and opportunities,, Trends Biotechnol., 24 (2006), 305. doi: 10.1016/j.tibtech.2006.04.008.

[20]

M. E. Bianchi, DAMPs, PAMPs and alarmins: all we need to know about danger,, J. Leukoc Biol., 81 (2007), 1. doi: 10.1189/jlb.0306164.

[21]

O. O. Bilukha and N. Rosenstein, Prevention and control of meningococcal disease,, Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep., 54 (2005), 1.

[22]

R. Bock, Plastid biotechnology: prospects for herbicide and insect resistance, metabolic engineering and molecular farming,, Curr. Opin. Biotechnol, 18 (2007), 100. doi: 10.1016/j.copbio.2006.12.001.

[23]

B. Bottazzi, A. Doni, C. Garlanda and A. Mantovani, An integrated view of humoral innate immunity: Pentraxins as a paradigm,, Annu. Rev. Immunol., 28 (2010), 157. doi: 10.1146/annurev-immunol-030409-101305.

[24]

D. J. Brayden, M. A. Jepson and A. W. Baird, Keynote review: Intestinal Peyer's patch M cells and oral vaccine targeting,, Drug Discov. Today, 10 (2005), 1145. doi: 10.1016/S1359-6446(05)03536-1.

[25]

S. Brighenti and J. Andersson, Induction and regulation of CD8+ cytolytic T cells in human tuberculosis and HIV infection,, Biochem. Biophys Res. Commun., 396 (2010), 50. doi: 10.1016/j.bbrc.2010.02.141.

[26]

I. H. Brown, D. J. Alexander, P. Chakraverty, P. A. Harris and R. J. Manvell, Isolation of an influenza A virus of unusual subtype (H1N7) from pigs in England, and the subsequent experimental transmission from pig to pig,, Vet. Microbiol., 39 (1994), 125. doi: 10.1016/0378-1135(94)90093-0.

[27]

I. H. Brown, P. A. Harris, J. W. McCauley and D. J. Alexander, Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype,, J. Gen. Virol., 79 (Pt 12) (1998), 2947.

[28]

A. Calmette, Preventive vaccination against tuberculosis with BCG,, Proc. R. Soc. Med., 24 (1931), 1481.

[29]

L. A. Campbell, C. C. Kuo and J. T. Grayston, Chlamydia pneumoniae and cardiovascular disease,, Emerg. Infect Dis., 4 (1998), 571. doi: 10.3201/eid0404.980407.

[30]

M. A. Campbell, H. A. Fitzgerald and P. C. Ronald, Engineering pathogen resistance in crop plants,, Transgenic Res., 11 (2002), 599. doi: 10.1023/A:1021109509953.

[31]

M. R. Castrucci, I. Donatelli, L. Sidoli, G. Barigazzi, Y. Kawaoka and R. G. Webster, Genetic reassortment between avian and human influenza A viruses in Italian pigs,, Virology, 193 (1993), 503. doi: 10.1006/viro.1993.1155.

[32]

T. M. Chambers, V. S. Hinshaw, Y. Kawaoka, B. C. Easterday and R. G. Webster, Influenza viral infection of swine in the United States 1988-1989,, Arch. Virol., 116 (1991), 261. doi: 10.1007/BF01319247.

[33]

Z. Chen, A. Aspelund, G. Kemble and H. Jin, Genetic mapping of the cold-adapted phenotype of B/Ann Arbor/1/66, the master donor virus for live attenuated influenza vaccines (FluMist),, Virology, 345 (2006), 416. doi: 10.1016/j.virol.2005.10.005.

[34]

K. M. Citron, BCG vaccination against tuberculosis: International perspectives,, Bmj, 306 (1993), 222.

[35]

H. F. Clark, P. A. Offit, R. W. Ellis, J. J. Eiden, D. Krah, A. R. Shaw, M. Pichichero, J. J. Treanor, F. E. Borian, L. M. Bell and S. A. Plotkin, The development of multivalent bovine rotavirus (strain WC3) reassortant vaccine for infants,, J. Infect Dis., 174 Suppl 1S (1996), 73.

[36]

J. Cohen and M. Enserink, Swine flu. after delays, WHO agrees: The 2009 pandemic has begun,, Science, 324 (2009), 1496. doi: 10.1126/science.324_1496.

[37]

G. A. Colditz, C. S. Berkey, F. Mosteller, T. F. Brewer, M. E. Wilson, E. Burdick and H. V. Fineberg, The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: Meta-analyses of the published literature,, Pediatrics, 96 (1995), 29.

[38]

D. B. Collinge, H. J. Jorgensen, O. S. Lund and M. F. Lyngkjaer, Engineering pathogen resistance in crop plants: Current trends and future prospects,, Annu. Rev. Phytopathol., 48 (2010), 269. doi: 10.1146/annurev-phyto-073009-114430.

[39]

G. Corradin and G. del Giudice, "Novel Adjuvants for Vaccines,", Current Medicinal Chemistry Anti-inflammatory and anti-allergy agents 4, (2005).

[40]

R. Curtiss, 3rd, W. Xin, Y. Li, W. Kong, S. Y. Wanda, B. Gunn and S. Wang, New technologies in using recombinant attenuated Salmonella vaccine vectors,, Crit. Rev. Immunol., 30 (2010), 255.

[41]

G. De Becker, V. Moulin, B. Pajak, C. Bruck, M. Francotte, C. Thiriart, J. Urbain and M. Moser, The adjuvant monophosphoryl lipid A increases the function of antigen-presenting cells,, Int. Immunol., 12 (2000), 807. doi: 10.1093/intimm/12.6.807.

[42]

P. Delves, S. Martin, D. Burton and I. Roitt, "Essential Immunology,", 11th ed. Wiley-Blackwell, (2006).

[43]

J. Diamond, "Guns, Gems and Steel: The Fates of Human Societies,", 1st ed., (1997).

[44]

R. Dommett, M. Zilbauer, J. T. George and M. Bajaj-Elliott, Innate immune defence in the human gastrointestinal tract,, Mol. Immunol., 42 (2005), 903. doi: 10.1016/j.molimm.2004.12.004.

[45]

M. L. Duran-Reynals, "The Fever Bark Tree: The Pageant of Quinine,", Doubleday, (1946).

[46]

J. L. Ebersole, M. A. Taubman, D. J. Smith and J. M. Goodson, Gingival crevicular fluid antibody to oral microorganisms. I. Method of collection and analysis of antibody,, J. Periodontal Res., 19 (1984), 124. doi: 10.1111/j.1600-0765.1984.tb00801.x.

[47]

P. Ehrlich, Ueber moderne Chemotherapie. Vortrag gehalten in der X,, Tagung der Deutschen Dermatologischen Gesellschaft. Akademische Verlagsgesellschaft m.b.H., (1908).

[48]

T. C. Elleman, A. A. Azad and C. W. Ward, Neuraminidase gene from the early Asian strain of human influenza virus, A/RI/5-/57 (H2N2),, Nucleic Acids Res., 10 (1982), 7005. doi: 10.1093/nar/10.21.7005.

[49]

L. Epstein and S. Bassein, Patterns of pesticide use in California and the implications for strategies for reduction of pesticides,, Annu. Rev. Phytopathol., 41 (2003), 351. doi: 10.1146/annurev.phyto.41.052002.095612.

[50]

N. Ferry, M. G. Edwards, J. A. Gatehouse and A. M. Gatehouse, Plant-insect interactions: molecular approaches to insect resistance,, Curr. Opin. Biotechnol., 15 (2004), 155. doi: 10.1016/j.copbio.2004.01.008.

[51]

R. H. Ffrench-Constant, P. J. Daborn and G. Le Goff, The genetics and genomics of insecticide resistance,, Trends Genet., 20 (2004), 163. doi: 10.1016/j.tig.2004.01.003.

[52]

A. Fleming, On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenza,, Brit. J. Exp. Path., 10 (1929), 226.

[53]

J. E. Galen and M. M. Levine, Can a 'flawless' live vector vaccine strain be engineered?, Trends Microbiol., 9 (2001), 372. doi: 10.1016/S0966-842X(01)02096-0.

[54]

L. Garrett, "The Coming Plague: Newly Emerging Diseases in a World Out of Balance,", 1st ed. Penguin, (1995).

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