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AAPS PharmSciTech

, 20:42 | Cite as

Stability of Vaccines

  • N. Dumpa
  • K. Goel
  • Yuhan Guo
  • H. McFall
  • Amit Raviraj Pillai
  • Ashay Shukla
  • M. A. Repka
  • S. Narasimha MurthyEmail author
Mini-Review Theme: Stability of Pharmaceutical Excipients
  • 170 Downloads
Part of the following topical collections:
  1. Theme: Stability of Pharmaceutical Excipients

Abstract

Vaccines are considered the most economical and effective preventive measure against most deadly infectious diseases. Vaccines help protect around three million lives every year, but hundreds of thousands of lives are lost due to the instability of vaccines. This review discusses the various types of instability observed, while manufacturing, storing, and distributing vaccines. It describes the specific stability problems associated with each type of vaccine. This review also discusses the various measures adopted to overcome these instability problems. Vaccines are classified based on their components, and this review discusses how these preventive measures relate to each type of vaccine. This review also includes certain case studies that illustrate various approaches to improve vaccine stability. Last, this review provides insight on prospective methods for developing more stable vaccines.

KEY WORDS

vaccine stability attenuated protein antigen 

Notes

References

  1. 1.
    Rexroad J, Wiethoff CM, Jones LS, Middaugh CR. Lyophilization and the thermostability of vaccines. Cell Preserv Technol. 2002;1:91–104.Google Scholar
  2. 2.
    Wang G, Li X, Mo L, Song Z, Chen W, Deng Y, et al. Eggshell-inspired biomineralization generates vaccines that do not require refrigeration. Angew Chem. 2012a;124:10728–31.Google Scholar
  3. 3.
    Alcock R, Cottingham MG, Rollier CS, Furze J, De Costa SD, Hanlon M, et al. Long-term thermostabilization of live poxviral and adenoviral vaccine vectors at supraphysiological temperatures in carbohydrate glass. Sci Transl Med. 2010;2:19ra12.PubMedGoogle Scholar
  4. 4.
    McGhee JR, Mestecky J, Dertzbaugh MT, Eldridge JH, Hirasawa M, Kiyono H. The mucosal immune system: from fundamental concepts to vaccine development. Vaccine. 1992;10:75–88.PubMedGoogle Scholar
  5. 5.
    Shata MT, Stevceva L, Agwale S, Lewis GK, Hone DM. Recent advances with recombinant bacterial vaccine vectors. Mol Med Today. 2000;6:66–71.PubMedGoogle Scholar
  6. 6.
    Corbel MJ. Reasons for instability of bacterial vaccines. Dev Biol Stand. 1996;87:113–24.PubMedGoogle Scholar
  7. 7.
    Ohtake S, Martin R, Saxena A, Pham B, Chiueh G, Osorio M, et al. Room temperature stabilization of oral, live attenuated Salmonella enterica serovar Typhi-vectored vaccines. Vaccine. 2011;29:2761–71.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Germanier R, Fuer E. Isolation and characterization of Gal E mutant Ty 21a of Salmonella Typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis. 1975;131:553–8.PubMedGoogle Scholar
  9. 9.
    Germanier R, Fürer E. Characteristics of the attenuated oral vaccine strain “S. Typhi” Ty 21a. Dev Biol Stand. 1982;53:3–7.Google Scholar
  10. 10.
    Kopecko DJ, Sieber H, Ures JA, Furer A, Schlup J, Knof U, et al. Genetic stability of vaccine strain Salmonella Typhi Ty21a over 25 years. Int J Med Microbiol. 2009;299:233–46.PubMedGoogle Scholar
  11. 11.
    Moyle PM, Toth I. Self-adjuvanting lipopeptide vaccines. Curr Med Chem. 2008;15:506–16.PubMedGoogle Scholar
  12. 12.
    Kumru OS, Joshi SB, Smith DE, Middaugh CR, Prusik T, Volkin DB. Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies. Biologicals. 2014;42:237–59.PubMedGoogle Scholar
  13. 13.
    Demento SL, Siefert AL, Bandyopadhyay A, Sharp FA, Fahmy TM. Pathogen-associated molecular patterns on biomaterials: a paradigm for engineering new vaccines. Trends Biotechnol. 2011;29:294–306.PubMedGoogle Scholar
  14. 14.
    Foged C, Hansen J, Agger EM. License to kill: formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems. Eur J Pharm Sci. 2012;45:482–91.PubMedGoogle Scholar
  15. 15.
    Lindblad EB. Aluminium adjuvants—in retrospect and prospect. Vaccine. 2004;22:3658–68.PubMedGoogle Scholar
  16. 16.
    Mutwiri G, Gerdts V, Littel v D, van den Hurk S, Auray G, Eng N, et al. Combination adjuvants: the next generation of adjuvants? Expert Rev Vaccines. 2011;10:95–107.PubMedGoogle Scholar
  17. 17.
    Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12:509–17.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Oyston P, Robinson K. The current challenges for vaccine development. J Med Microbiol. 2012;61:889–94.PubMedGoogle Scholar
  19. 19.
    McNeela E, Lavelle E. Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination, mucosal vaccines. Berlin: Springer; 2011. p. 75–99.Google Scholar
  20. 20.
    Ghosh TK, Mickelson DJ, Solberg JC, Lipson KE, Inglefield JR, Alkan SS. TLR-TLR cross talk in human PBMC resulting in synergistic and antagonistic regulation of type-1 and 2 interferons, IL-12 and TNF-alpha. Int Immunopharmacol. 2007;7:1111–21.PubMedGoogle Scholar
  21. 21.
    Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004;82:488–96.PubMedGoogle Scholar
  22. 22.
    Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19:1597–608.PubMedGoogle Scholar
  23. 23.
    Leleux J, Roy K. Micro and nanoparticle-based delivery systems for vaccine immunotherapy: an immunological and materials perspective. Adv Healthc Mater. 2013;2:72–94.PubMedGoogle Scholar
  24. 24.
    Sahdev P, Ochyl LJ, Moon JJ. Biomaterials for nanoparticle vaccine delivery systems. Pharm Res. 2014;31:2563–82.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Harde H, Agrawal AK, Jain S. Tetanus toxoids loaded glucomannosylated chitosan based nanohoming vaccine adjuvant with improved oral stability and immunostimulatory response. Pharm Res. 2015;32:122–34.PubMedGoogle Scholar
  26. 26.
    Juan-Giner A, Domicent C, Langendorf C, Roper MH, Baoundoh P, Fermon F, et al. A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain. Vaccine. 2014;32:6220–6.PubMedGoogle Scholar
  27. 27.
    Jain NK, Roy I. Accelerated stability studies for moisture-induced aggregation of tetanus toxoid. Pharm Res. 2011;28:626–39.PubMedGoogle Scholar
  28. 28.
    Jiang W, Schwendeman SP. Formaldehyde-mediated aggregation of protein antigens: comparison of untreated and formalinized model antigens. Biotechnol Bioeng. 2000;70:507–17.PubMedGoogle Scholar
  29. 29.
    Jain NK, Jetani HC, Roy I. Nucleic acid aptamers as stabilizers of proteins: the stability of tetanus toxoid. Pharm Res. 2013;30:1871–82.PubMedGoogle Scholar
  30. 30.
    Jain S, Harde H, Indulkar A, Agrawal AK. Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration. Nanomedicine. 2014;10:431–40.PubMedGoogle Scholar
  31. 31.
    Powell AJ, Little CB, Hughes CE. Low molecular weight isoforms of the aggrecanases are responsible for the cytokine-induced proteolysis of aggrecan in a porcine chondrocyte culture system. Arthritis Rheum. 2007;56:3010–9.PubMedGoogle Scholar
  32. 32.
    Verma R, Oania RS, Kolawa NJ, Deshaies RJ. Cdc48/p97 promotes degradation of aberrant nascent polypeptides bound to the ribosome. Elife. 2013;2:e00308.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Zomber G, Reuveny S, Garti N, Shafferman A, Elhanany E. Effects of spontaneous deamidation on the cytotoxic activity of the Bacillus anthracis protective antigen. J Biol Chem. 2005;280:39897–906.PubMedGoogle Scholar
  34. 34.
    Jones RM, Burke M, Dubose D, Chichester JA, Manceva S, Horsey A, et al. Stability and pre-formulation development of a plant-produced anthrax vaccine candidate. Vaccine. 2017;35:5463–70.PubMedGoogle Scholar
  35. 35.
    Jiang G, Joshi SB, Peek LJ, Brandau DT, Huang J, Ferriter MS, et al. Anthrax vaccine powder formulations for nasal mucosal delivery. J Pharm Sci. 2006;95:80–96.PubMedGoogle Scholar
  36. 36.
    Mikszta JA, Sullivan VJ, Dean C, Waterston AM, Alarcon JB, Dekker JP 3rd, et al. Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms. J Infect Dis. 2005;191:278–88.PubMedGoogle Scholar
  37. 37.
    Wang SH, Kirwan SM, Abraham SN, Staats HF, Hickey AJ. Stable dry powder formulation for nasal delivery of anthrax vaccine. J Pharm Sci. 2012b;101:31–47.PubMedGoogle Scholar
  38. 38.
    Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher A, Davis S. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev. 2001;51:81–96.PubMedGoogle Scholar
  39. 39.
    Kemble G, Greenberg H. Novel generations of influenza vaccines. Vaccine. 2003;21:1789–95.PubMedGoogle Scholar
  40. 40.
    Flick-Smith HC, Eyles JE, Hebdon R, Waters EL, Beedham RJ, Stagg TJ, et al. Mucosal or parenteral administration of microsphere-associated Bacillus anthracis protective antigen protects against anthrax infection in mice. Infect Immun. 2002;70:2022–8.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Lauring AS, Jones JO, Andino R. Rationalizing the development of live attenuated virus vaccines. Nat Biotechnol. 2010;28:573–9.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Burke, C.J., Hsu, T., Volkin, D.B., 1999. Formulation, stability, and delivery of live attenuated vaccines for human use. Critical Reviews™ in Therapeutic Drug Carrier Systems 16:1–83.Google Scholar
  43. 43.
    Chen D, Kristensen D. Opportunities and challenges of developing thermostable vaccines. Expert Rev Vaccines. 2009;8:547–57.PubMedGoogle Scholar
  44. 44.
    Cleland JL, Powell MF, Shire SJ. The development of stable protein formulations: a close look at protein aggregation, deamidation, and oxidation. Crit Rev Ther Drug Carrier Syst. 1993;10:307–77.PubMedGoogle Scholar
  45. 45.
    Volkin DB, Mach H, Middaugh CR. Degradative covalent reactions important to protein stability. Mol Biotechnol. 1997;8:105–22.PubMedGoogle Scholar
  46. 46.
    Saboo S, Tumban E, Peabody J, Wafula D, Peabody DS, Chackerian B, et al. Optimized formulation of a thermostable spray-dried virus-like particle vaccine against human papillomavirus. Mol Pharm. 2016;13:1646–55.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Kraan H, van Herpen P, Kersten G, Amorij JP. Development of thermostable lyophilized inactivated polio vaccine. Pharm Res. 2014;31:2618–29.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Dorval BL, Chow M, Klibanov AM. Lysine and other diamines dramatically stabilize poliovirus against thermoinactivation. Biotechnol Bioeng. 1990;35:1051–4.Google Scholar
  49. 49.
    Ofori-Anyinam O, Vrijsen R, Kronenberger P, Boeye A. Heat stabilized, infectious poliovirus. Vaccine. 1995;13:983–6.Google Scholar
  50. 50.
    Crainic R, Wu R, Otelea D, Georgescu M, Delpeyroux F, Guillot S, et al. The replacement of water with deuterium oxide significantly improves the thermal stability of the oral poliovirus vaccine. Dev Biol Stand. 1996;87:161–6.Google Scholar
  51. 51.
    Berge TO, Jewett RL, Blair WO. Preservation of enteroviruses by freeze drying. Appl Microbiol. 1971;22:850–3.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Ferreira E, Mendes YS, Silva JL, Galler R, Oliveira AC, Freire MS, et al. Effects of hydrostatic pressure on the stability and thermostability of poliovirus: a new method for vaccine preservation. Vaccine. 2009;27:5332–7.PubMedGoogle Scholar
  53. 53.
    Amorij JP, Huckriede A, Wilschut J, Frijlink HW, Hinrichs WL. Development of stable influenza vaccine powder formulations: challenges and possibilities. Pharm Res. 2008;25:1256–73.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25–44.PubMedGoogle Scholar
  55. 55.
    Neuzil KM, Hohlbein C, Zhu Y. Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Arch Pediatr Adolesc Med. 2002;156:986–91.PubMedGoogle Scholar
  56. 56.
    Wright PF, Webster RG. Orthomyxoviruses. In: Fields BN, Knipe DM, editors. Fields Virology, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 1533–1579.Google Scholar
  57. 57.
    Kamerzell TJ, Esfandiary R, Joshi SB, Middaugh CR, Volkin DB. Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. Adv Drug Deliv Rev. 2011;63:1118–59.PubMedGoogle Scholar
  58. 58.
    White JA, Estrada M, Flood EA, Mahmood K, Dhere R, Chen D. Development of a stable liquid formulation of live attenuated influenza vaccine. Vaccine. 2016;34:3676–83.PubMedPubMedCentralGoogle Scholar
  59. 59.
    World health Organization, 2006. Guidelines on stability evaluation of vaccines, WHO/BS/062049.Google Scholar
  60. 60.
    Ohtake S, Martin RA, Yee L, Chen D, Kristensen DD, Lechuga-Ballesteros D, et al. Heat-stable measles vaccine produced by spray drying. Vaccine. 2010;28:1275–84.PubMedGoogle Scholar
  61. 61.
    Edens C, Collins ML, Ayers J, Rota PA, Prausnitz MR. Measles vaccination using a microneedle patch. Vaccine. 2013;31:3403–9.PubMedGoogle Scholar
  62. 62.
    Zhang J, Pritchard E, Hu X, Valentin T, Panilaitis B, Omenetto FG, et al. Stabilization of vaccines and antibiotics in silk and eliminating the cold chain. Proc Natl Acad Sci U S A. 2012;109:11981–6.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Ghobadloo SM, Balcerzak AK, Gargaun A, Muharemagic D, Mironov GG, Capicciotti CJ, et al. Carbohydrate-based ice recrystallization inhibitors increase infectivity and thermostability of viral vectors. Sci Rep. 2014;4:5903.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Nascimento I, Leite L. Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res. 2012;45:1102–11.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Michel ML, Tiollais P. Hepatitis B vaccines: protective efficacy and therapeutic potential. Pathol Biol (Paris). 2010;58:288–95.Google Scholar
  66. 66.
    Beutels P. Economic evaluations of hepatitis B immunization: a global review of recent studies (1994–2000). Health Econ. 2001;10:751–74.PubMedGoogle Scholar
  67. 67.
    Maynard JE, Kane MA, Hadler SC. Global control of hepatitis B through vaccination: role of hepatitis B vaccine in the expanded programme on immunization. Clin Infect Dis. 1989;11:S574–8.Google Scholar
  68. 68.
    Van Damme P, Cramm M, Safary A, Vandepapeliere P, Meheus A. Heat stability of a recombinant DNA hepatitis B vaccine. Vaccine. 1992;10:366–7.PubMedGoogle Scholar
  69. 69.
    Zapata MI, Feldkamp JR, Peck GE, White JL, Hem SL. Mechanism of freeze-thaw instability of aluminum hydroxycarbonate and magnesium hydroxide gels. J Pharm Sci. 1984;73:3–8.PubMedGoogle Scholar
  70. 70.
    Diminsky D, Moav N, Gorecki M, Barenholz Y. Physical, chemical and immunological stability of CHO-derived hepatitis B surface antigen (HBsAg) particles. Vaccine. 1999;18:3–17.PubMedGoogle Scholar
  71. 71.
    Brandau DT, Jones LS, Wiethoff CM, Rexroad J, Middaugh CR. Thermal stability of vaccines. J Pharm Sci. 2003;92:218–31.PubMedGoogle Scholar
  72. 72.
    Jezek J, Chen D, Watson L, Crawford J, Perkins S, Tyagi A, et al. A heat-stable hepatitis B vaccine formulation. Hum Vaccin. 2009;5:529–35.PubMedGoogle Scholar
  73. 73.
    Braun LJ, Jezek J, Peterson S, Tyagi A, Perkins S, Sylvester D, et al. Characterization of a thermostable hepatitis B vaccine formulation. Vaccine. 2009;27:4609–14.PubMedGoogle Scholar
  74. 74.
    Tonnis WF, Amorij JP, Vreeman MA, Frijlink HW, Kersten GF, Hinrichs WL. Improved storage stability and immunogenicity of hepatitis B vaccine after spray-freeze drying in presence of sugars. Eur J Pharm Sci. 2014;55:36–45.PubMedGoogle Scholar
  75. 75.
    Brotherton JM, Ogilvie GS. Current status of human papillomavirus vaccination. Curr Opin Oncol. 2015;27:399–404.PubMedGoogle Scholar
  76. 76.
    Govan VA. A novel vaccine for cervical cancer: quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (Gardasil®). Ther Clin Risk Manag. 2008;4:65–70.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Pérez O, Batista-Duharte A, González E, Zayas C, Balboa J, Cuello M, et al. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations. Braz J Med Biol Res. 2012;45:681–92.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Shi L, Sanyal G, Ni A, Luo Z, Doshna S, Wang B, et al. Stabilization of human papillomavirus virus-like particles by non-ionic surfactants. J Pharm Sci. 2005;94:1538–51.PubMedGoogle Scholar
  79. 79.
    Fausch SC, Da Silva DM, Eiben GL, Le Poole IC, Kast WM. HPV protein/peptide vaccines: from animal models to clinical trials. Front Biosci. 2003;8:s81–91.PubMedGoogle Scholar
  80. 80.
    Gerard C, Baudson N, Kraemer K, Bruck C, Garcon N, Paterson Y, et al. Therapeutic potential of protein and adjuvant vaccinations on tumour growth. Vaccine. 2001;19:2583–9.PubMedGoogle Scholar
  81. 81.
    Hung CF, Ma B, Monie A, Tsen SW, Wu TC. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther. 2008;8:421–39.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Bam NB, Cleland JL, Yang J, Manning MC, Carpenter JF, Kelley RF, et al. Tween protects recombinant human growth hormone against agitation-induced damage via hydrophobic interactions. J Pharm Sci. 1998;87:1554–9.PubMedGoogle Scholar
  83. 83.
    Hageman M. Stability of protein pharmaceuticals. Part A. Chemical and physical pathways of protein degradation. In: Ahern TJ, Manning MC, editors. . New York: Plenum Press; 1994. p. 273–309.Google Scholar
  84. 84.
    Avis KE, Wu VL. Biotechnology and biopharmaceutical manufacturing, processing, and preservation. Boca Raton: CRC Press; 1996.Google Scholar
  85. 85.
    Avery OT, Goebel WF. Chemo-immunological studies on conjugated carbohydrate-proteins : II. Immunological specificity of synthetic sugar-protein antigens. J Exp Med. 1929;50:533–50.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Black S, Shinefield H, Fireman B, Lewis E, Ray P, Hansen JR, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J. 2000;19:187–95.PubMedGoogle Scholar
  87. 87.
    Finn A. Bacterial polysaccharide-protein conjugate vaccines. Br Med Bull. 2004;70:1–14.PubMedGoogle Scholar
  88. 88.
    Koskela M, Leinonen M, Haiva VM, Timonen M, Makela PH. First and second dose antibody responses to pneumococcal polysaccharide vaccine in infants. Pediatr Infect Dis. 1986;5:45–50.PubMedGoogle Scholar
  89. 89.
    Lindberg AA. Glycoprotein conjugate vaccines. Vaccine. 1999;17(Suppl 2):S28–36.PubMedGoogle Scholar
  90. 90.
    Peltola H, Kayhty H, Virtanen M, Makela PH. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med. 1984;310:1561–6.PubMedGoogle Scholar
  91. 91.
    Richmond P, Borrow R, Findlow J, Martin S, Thornton C, Cartwright K, et al. Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains. Infect Immun. 2001;69:2378–82.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Wang JF, Caugant DA, Morelli G, Koumare B, Achtman M. Antigenic and epidemiologic properties of the ET-37 complex of Neisseria meningitidis. J Infect Dis. 1993;167:1320–9.PubMedGoogle Scholar
  93. 93.
    Friedrich F. Rare adverse events associated with oral poliovirus vaccine in Brazil. Braz J Med Biol Res. 1997;30:695–703.PubMedGoogle Scholar
  94. 94.
    Minor P. Vaccine-derived poliovirus (VDPV): impact on poliomyelitis eradication. Vaccine. 2009;27:2649–52.PubMedGoogle Scholar
  95. 95.
    Salas-Peraza D, Avila-Agüero ML, Morice-Trejos A. Switching from OPV to IPV: are we behind the schedule in Latin America? Expert Rev Vaccines. 2010;9:475–83.PubMedGoogle Scholar
  96. 96.
    Atkinson W, Wolfe S, Hamborsky J. Epidemiology and prevention of vaccine-preventable diseases. Washington: Public Health Foundation; 2011.Google Scholar
  97. 97.
    Kristensen D. Summary of stability data for licensed vaccines. Seattle: PATH; 2012.Google Scholar
  98. 98.
    Qi W, Zeng Y, Orgel S, Francon A, Kim JH, Randolph TW, et al. Preformulation study of highly purified inactivated polio vaccine, serotype 3. J Pharm Sci. 2014;103:140–51.PubMedGoogle Scholar
  99. 99.
    Tzeng SY, Guarecuco R, McHugh KJ, Rose S, Rosenberg EM, Zeng Y, et al. Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release. J Control Release. 2016;233:101–13.Google Scholar
  100. 100.
    Kraan H, Ploemen I, van de Wijdeven G, Que I, Lowik C, Kersten G, et al. Alternative delivery of a thermostable inactivated polio vaccine. Vaccine. 2015;33:2030–7.Google Scholar
  101. 101.
    Edwards KM, Meade BD, Decker MD, Reed MF, Rennels MB, Steinhoff MC, et al. Comparison of 13 acellular pertussis vaccines: overview and serologic response. Pediatrics. 1996;97:784.Google Scholar
  102. 102.
    Skibinski DA, Baudner BC, Singh M, O'Hagan DT. Combination vaccines. J Glob Infect Dis. 2011;3:63–72.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Jivapisarnpong T. Combined vaccines—case study. Biologicals. 2009;37:416.PubMedGoogle Scholar
  104. 104.
    Dobbelaer R, Pfleiderer M, Haase M, Griffiths E, Knezevic I, Merkle A, et al. Guidelines on stability evaluation of vaccines. Biologicals. 2009;37:424–34 discussion 421-423.PubMedGoogle Scholar
  105. 105.
    Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet. 1999;354:2063–8.PubMedGoogle Scholar
  106. 106.
    Schmitt, H.J., 1995. Immunogenicity and reactogenicity of two Haemophilus influenzae type b tetanus conjugate vaccines admninistered by reconstituting with diphtheria-tetanus-acellular pertussis vaccine or given as separate injections (abstract G63), 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco.Google Scholar
  107. 107.
    Slack MH, Schapira D, Thwaites RJ, Burrage M, Southern J, Andrews N, et al. Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines. J Infect Dis. 2001;184:1617–20.PubMedGoogle Scholar
  108. 108.
    Decker MD. Principles of pediatric combination vaccines and practical issues related to use in clinical practice. Pediatr Infect Dis J. 2001;20:S10–8.PubMedGoogle Scholar
  109. 109.
    Schmitt HJ, Knuf M, Ortiz E, Sänger R, Uwamwezi MC, Kaufhold A. Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. J Pediatr. 2000;137:304–12.PubMedGoogle Scholar
  110. 110.
    Dagan R, Poolman JT, Zepp F. Combination vaccines containing DTPa-Hib: impact of IPV and coadministration of CRM197 conjugates. Expert Rev Vaccines. 2008;7:97–115.PubMedGoogle Scholar
  111. 111.
    Jatana SK, Nair M. Combination vaccines. Med J Armed Forces India. 2007;63:167–71.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Zeng Y, Fan H, Chiueh G, Pham B, Martin R, Lechuga-Ballesteros D, et al. Towards development of stable formulations of a live attenuated bacterial vaccine: a preformulation study facilitated by a biophysical approach. Hum Vaccin. 2009;5:322–31.PubMedGoogle Scholar
  113. 113.
    Rao YU, William J, Kalyanaraman VR. A study of the stability of the pertussis component of diphtheria-tetanus-pertussis (DTP) vaccines. J Biol Stand. 1985;13:267–70.PubMedGoogle Scholar
  114. 114.
    Galazka A, Milstien J, Zaffran M. Thermostability of vaccines: global programme for vaccines and immunization. Geneva: World Health Organization; 1998.Google Scholar

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© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • N. Dumpa
    • 1
  • K. Goel
    • 1
  • Yuhan Guo
    • 1
  • H. McFall
    • 1
  • Amit Raviraj Pillai
    • 1
  • Ashay Shukla
    • 1
  • M. A. Repka
    • 1
  • S. Narasimha Murthy
    • 1
    Email author
  1. 1.Department of Pharmaceutics and Drug DeliveryThe University of MississippiUniversityUSA

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