Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B

详细信息    查看全文

• 作者：Caridad Zayas (1)
  Domingo González (1)
  Reinaldo Acevedo (1)
  Judith del Campo (1)
  Miriam Lastre (1)
  Elizabeth González (1)
  Belkis Romeu (1)
  Maribel Cuello (1)
  Julio Balboa (1)
  Osmir Cabrera (1)
  Luisa Guilherme (2)
  Oliver Pérez (1)
  
• 刊名：BMC Immunology
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：14
• 期：1-supp
• 全文大小：129KB
• 参考文献：1. Gar?on N, Chomez P, Van Mechelen : GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. / Expert Rev Vaccines 2007.,6(5):
  2. Pérez O, Lastre M, Cabrera O, del Campo J, Bracho G, Cuello M, Balboa J, Acevedo R, Zayas C, Gil D, / et al.: New Vaccines Require Potent Adjuvants like AFPL1 and AFCo1. / Scandinavian Journal of Immunology 2007, 66:271-77. CrossRef
  3. Campa C, Sierra VG, Gutiérrez MM, Biset G, García LG, Puentes G, Sampedro M, Sotolongo F, Le Riverend E, Galguera M, / et al.: Methods of producing Neissseria meningitidis B vaccine. / USPTO 1997. number 5,597,572
  4. Zayas C, Bracho G, Lastre M, González D, Gil D, Acevedo R, del Campo J, Taboada C, Solís RL, Barberá R, Pérez O: Scale up of proteoliposome derived cochleate production. / Vaccine 2006,24(S2):S2-4.
  5. Meltzer T, Jornitz MW: Filtration in the biopharmaceutical industry. / Marcel Dekker Inc 1998.
  6. Ferriol X, García AG, Ochoa R, Bravo I, Blanco R, Estrada E: Validación de un ELISA para la cuantificación de IgG humana anti proteína de Neisseria meningitidis serogrupo B. / Revista Cubana de Medicina Tropical 1999,51(2):99-05.
  7. Neurath MF, Finotto S, Glimcher L: The role of Th1 /Th2 polarization in mucosal immunity. / Nature Medicine 2002,8(6):567-73. CrossRef
  8. del Campo J, Zayas C, Romeu B, Acevedo R, González E, Bracho G, Cuello M, Cabrera O, Balboa J, Lastre M: Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses. / Methods 2009,49(4):301-08. CrossRef
  9. Kidd P: Th1/Th2 balance: the hypothesis, STI Limitations, and Implications for health and disease. / Altern Med Rev 2003,8(3):223-6.
  10. Infante JF, Sifontes S, Pérez V, Bracho G, Hernández T, Zayas C, López Y, Díaz D, Acevedo R, Rodríguez N, / et al.: Ensayo de inmunogenicidad y toxicidad local del cocleato de Neisseria meningitidis en ratas Sprague Dawley. / Vaccimonitor 2010,18(1):1-.
  11. Mora D, Dominguez R, Duke E, Martínez L, Escoto J, Jacobo OL: Adjuvants: Present regulatory challenges. / Vaccine 2006,24(S2):S2-0.
  
• 作者单位：Caridad Zayas (1)
  Domingo González (1)
  Reinaldo Acevedo (1)
  Judith del Campo (1)
  Miriam Lastre (1)
  Elizabeth González (1)
  Belkis Romeu (1)
  Maribel Cuello (1)
  Julio Balboa (1)
  Osmir Cabrera (1)
  Luisa Guilherme (2)
  Oliver Pérez (1)
  
  1. Finlay Institute, Ave. 27 No. 19805, La Lisa, Havana, AP. 16017, CP11600, Cuba
  2. Heart Institute (InCor) of Sao Paulo, Kragujevac, Brazil
  
• ISSN：1471-2172

文摘

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m2 area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.