Formulation Approaches and Strategies for Vaccines and Adjuvants

In order to create safe and efficacious vaccines, formulations that confer stability must generally be developed. In this chapter, formulation considerations consisting of solution conditions, particles, delivery route, endotoxin level, and preservatives will be covered along with the addition of adjuvants currently approved for use in vaccines and adjuvants currently being researched. Methods to increase vaccine stability and analytical techniques used to monitor vaccines will be discussed.

[1]  S. Ascarateil,et al.  The use of oil adjuvants in therapeutic vaccines. , 2006, Vaccine.

[2]  Matthias Müller,et al.  Influenza virosomes as vaccine adjuvant and carrier system , 2011, Expert review of vaccines.

[3]  L. Kaminskas,et al.  New developments in dry powder pulmonary vaccine delivery. , 2011, Trends in biotechnology.

[4]  S. Joshi,et al.  Multidimensional methods for the formulation of biopharmaceuticals and vaccines. , 2011, Journal of pharmaceutical sciences.

[5]  S. Bertholet,et al.  New horizons in adjuvants for vaccine development. , 2009, Trends in immunology.

[6]  G. Ott,et al.  Recent advances in vaccine adjuvants: the development of MF59 emulsion and polymeric microparticles. , 1997, Molecular medicine today.

[7]  R. Couch,et al.  Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant. , 2007, Vaccine.

[8]  R. Borchardt,et al.  Stability of Protein Pharmaceuticals , 1989, Pharmaceutical Research.

[9]  C. Kensil,et al.  Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. , 1991, Journal of immunology.

[10]  Susan Hershenson,et al.  Practical approaches to protein formulation development. , 2002, Pharmaceutical biotechnology.

[11]  Wei Wang,et al.  Antibody structure, instability, and formulation. , 2007, Journal of pharmaceutical sciences.

[12]  B. D. De Geest,et al.  Crossing the barrier: Targeting epithelial receptors for enhanced oral vaccine delivery. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[13]  C. Bode,et al.  TLR-based immune adjuvants. , 2011, Vaccine.

[14]  Dexiang Chen,et al.  Vaccines with aluminum-containing adjuvants: optimizing vaccine efficacy and thermal stability. , 2011, Journal of pharmaceutical sciences.

[15]  Bali Pulendran,et al.  Immunological mechanisms of vaccination , 2011, Nature Immunology.

[16]  B. Narasimhan,et al.  Vaccine adjuvants: current challenges and future approaches. , 2009, Journal of pharmaceutical sciences.

[17]  Manmohan J. Singh,et al.  Effect of the strength of adsorption of HIV 1 SF162dV2gp140 to aluminum-containing adjuvants on the immune response. , 2011, Journal of pharmaceutical sciences.

[18]  K. Shakesheff,et al.  Formulations for delivery of therapeutic proteins , 2008, Biotechnology Letters.

[19]  D. Persing,et al.  Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents , 2004, Expert opinion on biological therapy.

[20]  M. Adams,et al.  Design and synthesis of potent Quillaja saponin vaccine adjuvants. , 2010, Journal of the American Chemical Society.

[21]  S. Nail,et al.  Development and Manufacture of Protein Pharmaceuticals , 2002, Pharmaceutical Biotechnology.

[22]  R. Rappuoli,et al.  MF59 adjuvant: the best insurance against influenza strain diversity , 2011, Expert review of vaccines.

[23]  K. Dalsgaard,et al.  Preparation and characterisation of quillaja saponin with less heterogeneity than Quil-A. , 2000, Vaccine.

[24]  Hongxiang Sun,et al.  ISCOMs and ISCOMATRIX. , 2009, Vaccine.

[25]  D. Montefiori,et al.  QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. , 2001, Vaccine.

[26]  C. Kensil,et al.  QS-21: a water-soluble triterpene glycoside adjuvant. , 1998, Expert opinion on investigational drugs.

[27]  D. Volkin,et al.  Preformulation studies--The next advance in aluminum adjuvant-containing vaccines. , 2010, Vaccine.

[28]  Manmohan J. Singh,et al.  A preliminary evaluation of alternative adjuvants to alum using a range of established and new generation vaccine antigens. , 2006, Vaccine.

[29]  R. Sitrin,et al.  Relationship between tightness of binding and immunogenicity in an aluminum-containing adjuvant-adsorbed hepatitis B vaccine. , 2009, Vaccine.

[30]  Michael J. Pikal,et al.  Rational Design of Stable Lyophilized Protein Formulations: Some Practical Advice , 1997, Pharmaceutical Research.

[31]  H. HogenEsch,et al.  Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants. , 2007, Vaccine.

[32]  Martin F. Bachmann,et al.  Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns , 2010, Nature Reviews Immunology.

[33]  C. Witham,et al.  A powder formulation of measles vaccine for aerosol delivery. , 2001, Vaccine.

[34]  G. Brazeau,et al.  Current perspectives on pain upon injection of drugs. , 1998, Journal of pharmaceutical sciences.

[35]  V. Kanchan,et al.  Interactions of antigen-loaded polylactide particles with macrophages and their correlation with the immune response. , 2007, Biomaterials.

[36]  B. Kerwin,et al.  Secondary structures of proteins adsorbed onto aluminum hydroxide: infrared spectroscopic analysis of proteins from low solution concentrations. , 2006, Analytical biochemistry.

[37]  François Spertini,et al.  A synthetic malaria vaccine elicits a potent CD8+ and CD4+ T lymphocyte immune response in humans. Implications for vaccination strategies , 2001, European journal of immunology.

[38]  J. Carpenter,et al.  Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution. , 2009, Journal of pharmaceutical sciences.

[39]  J. Carpenter,et al.  Inhibition of aggregation of aluminum hydroxide adjuvant during freezing and drying. , 2008, Journal of pharmaceutical sciences.

[40]  Michael V Sefton,et al.  Endotoxin: the uninvited guest. , 2005, Biomaterials.

[41]  Steven J Shire,et al.  Challenges in the development of high protein concentration formulations. , 2004, Journal of pharmaceutical sciences.

[42]  Daniel E. Otzen,et al.  Protein drug stability: a formulation challenge , 2005, Nature Reviews Drug Discovery.

[43]  J. White,et al.  Degree of antigen adsorption in the vaccine or interstitial fluid and its effect on the antibody response in rabbits. , 2001, Vaccine.

[44]  J. Donnelly,et al.  Mucosal adjuvants and delivery systems for protein‐, DNA‐ and RNA‐based vaccines , 2004, Immunology and cell biology.

[45]  N. Lycke From toxin to adjuvant: the rational design of a vaccine adjuvant vector, CTA1‐DD/ISCOM , 2004, Cellular microbiology.

[46]  Manmohan J. Singh,et al.  Acceptable levels of endotoxin in vaccine formulations during preclinical research. , 2011, Journal of pharmaceutical sciences.

[47]  Manmohan J. Singh,et al.  Aluminum adjuvant dose guidelines in vaccine formulation for preclinical evaluations. , 2012, Journal of pharmaceutical sciences.

[48]  M. Lievens,et al.  Safety and immunogenicity profile of an experimental hepatitis B vaccine adjuvanted with AS04. , 2004, Vaccine.

[49]  Theodore W Randolph,et al.  Influence of particle size and antigen binding on effectiveness of aluminum salt adjuvants in a model lysozyme vaccine. , 2008, Journal of pharmaceutical sciences.

[50]  S. Ascarateil,et al.  Montanide ISA 720 and 51: a new generation of water in oil emulsions as adjuvants for human vaccines , 2002, Expert review of vaccines.

[51]  Dexiang Chen,et al.  Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants. , 2009, Vaccine.

[52]  Y. Barenholz,et al.  Physical, chemical and immunological stability of CHO-derived hepatitis B surface antigen (HBsAg) particles. , 1999, Vaccine.

[53]  V. Vasudevan,et al.  Formulation development of protein dosage forms. , 2002, Pharmaceutical biotechnology.

[54]  N. Jacobsen,et al.  Isomerization and formulation stability of the vaccine adjuvant QS-21. , 1996, Journal of pharmaceutical sciences.

[55]  C. Wiethoff,et al.  Thermal stability of vaccines. , 2003, Journal of pharmaceutical sciences.

[56]  J. Arciniega,et al.  Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants. , 2005, Vaccine.

[57]  T. Mitchell,et al.  Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant , 2008, Cellular and Molecular Life Sciences.

[58]  Jan Holmgren,et al.  Mucosal immunity and vaccines , 2005, Nature Medicine.

[59]  D. Geier,et al.  The relative toxicity of compounds used as preservatives in vaccines and biologics. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[60]  Raymond C Rowe,et al.  Handbook of Pharmaceutical Excipients , 1994 .

[61]  Elly van Riet,et al.  Advances in transcutaneous vaccine delivery: do all ways lead to Rome? , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[62]  S. Gnjatic,et al.  Toll-Like Receptor Agonists: Are They Good Adjuvants? , 2010, Cancer journal.

[63]  H. Oettgen,et al.  GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. , 1995, Cancer research.

[64]  R. Kircheis,et al.  Immunogenicity of therapeutics: a matter of efficacy and safety , 2010, Expert opinion on drug discovery.

[65]  W. Hinrichs,et al.  Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities , 2008, Pharmaceutical Research.

[66]  P. Chomez,et al.  GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives , 2007, Expert review of vaccines.

[67]  C. Braun,et al.  Stabilizing formulations for inhalable powders of live-attenuated measles virus vaccine. , 2008, Journal of aerosol medicine and pulmonary drug delivery.

[68]  M. Green,et al.  Mechanism of immunopotentiation by aluminum-containing adjuvants elucidated by the relationship between antigen retention at the inoculation site and the immune response. , 2010, Vaccine.

[69]  Manmohan J. Singh,et al.  Endotoxin limits in formulations for preclinical research. , 2008, Journal of pharmaceutical sciences.

[70]  C. Gittleson,et al.  ISCOMATRIX™ vaccines: Safety in human clinical studies , 2010, Human vaccines.

[71]  Tim J Kamerzell,et al.  Protein-excipient interactions: mechanisms and biophysical characterization applied to protein formulation development. , 2011, Advanced drug delivery reviews.

[72]  G. Ayelet,et al.  Xerovac: an ultra rapid method for the dehydration and preservation of live attenuated Rinderpest and Peste des Petits ruminants vaccines. , 2000, Vaccine.

[73]  C. Mandl,et al.  Vaccines for the twenty-first century society , 2011, Nature Reviews Immunology.

[74]  Adalberto Pessoa,et al.  Methods of endotoxin removal from biological preparations: a review. , 2007, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[75]  Zhengrong Cui,et al.  Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses , 2010, Expert review of vaccines.

[76]  J. White,et al.  Predicting the adsorption of proteins by aluminium-containing adjuvants. , 1991, Vaccine.

[77]  Joe D. Cohen,et al.  A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. , 1997, The New England journal of medicine.

[78]  Jared S. Bee,et al.  Monoclonal antibody interactions with micro- and nanoparticles: adsorption, aggregation, and accelerated stress studies. , 2009, Journal of pharmaceutical sciences.

[79]  Ennio De Gregorio,et al.  The path to a successful vaccine adjuvant--'the long and winding road'. , 2009, Drug discovery today.

[80]  B. Spiessens,et al.  Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials , 2009, Human vaccines.

[81]  R. Rappuoli,et al.  New adjuvants for human vaccines. , 2010, Current opinion in immunology.

[82]  G. Haas,et al.  IRX-2 increases the T cell-specific immune response to protein/peptide vaccines. , 2010, Vaccine.

[83]  R. Neufeld,et al.  Systemic and Mucosal Delivery of Drugs within Polymeric Microparticles Produced by Spray Drying , 2010, BioDrugs.

[84]  D. Novicki,et al.  Safety of MF59 adjuvant. , 2008, Vaccine.

[85]  A. Thomas,et al.  Safety and Immunogenicity of a Recombinant Plasmodium falciparum AMA1 Malaria Vaccine Adjuvanted with Alhydrogel™, Montanide ISA 720 or AS02 , 2008, PloS one.

[86]  C Russell Middaugh,et al.  Preformulation studies as an essential guide to formulation development and manufacture of protein pharmaceuticals. , 2002, Pharmaceutical biotechnology.

[87]  G. Russell-Jones,et al.  Oral vaccine delivery. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[88]  M. Pearse,et al.  ISCOMATRIX adjuvant for antigen delivery. , 2005, Advanced drug delivery reviews.

[89]  A. Morin,et al.  Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine. , 2009, Journal of pharmaceutical sciences.

[90]  F. Vogel Improving vaccine performance with adjuvants. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[91]  Amber Haynes Fradkin,et al.  Glass particles as an adjuvant: a model for adverse immunogenicity of therapeutic proteins. , 2011, Journal of pharmaceutical sciences.

[92]  L. Peek,et al.  Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants. , 2007, Journal of pharmaceutical sciences.

[93]  J. Angel,et al.  CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults , 2005, AIDS.

[94]  P. Chomez,et al.  Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity. , 2011, Vaccine.