Vaccines, Blood & Biologics
Development, Evaluation and Improvement of Quality Control Methods for Bacterial Vaccines
Principal Investigator: Juan L. Arciniega, PhD
Office / Division / Lab: OVRR / DBPAP / LRSP
Immunization with safe and effective vaccines constitutes a critical component of a number of programs aimed to the prevention of infectious diseases, including those produced by the nefarious use of biological agents. Relevant and well-controlled tests to assess the safety, purity and potency of bacterial immunogens are important for maintaining the quality of licensed vaccines and evaluating new products. Our research program contributes to the development, evaluation and standardization of methods to assess the quality of bacterial vaccine products. Methods studied or developed in full or in part during our research may be used in house for regulatory purposes or offered to manufacturers as the basis for their own methods development program. During many years bioassay using animals has represented a cornerstone of vaccine testing. Although animal-based tests have been very useful for the evaluation of the potency and safety of vaccines, we have responded to government policy that encourages, when possible, reduction, refinement and replacement of animals. A component of our research program that is gaining importance is the use of rigorous scientific evaluation of alternatives to animal testing. Because the methods under development are intended to be used in support of regulatory decisions, needs for reference materials are identified during the process and, when appropriate, their production and standardization is coordinated. On the other hand, vaccines are used globally, and consequently international harmonization and standardization of relevant methods has become important for most products. Thus, continuous participation of the laboratory in harmonization efforts is not only warranted, but highly desirable.
We make use of recent advances in immunology, biochemistry and cell biology to design, standardize and validate bioassays that assess the purity, potency and safety of vaccines. When designing new assays or substituting traditional assays, we adhere to the philosophy of replacing, refining, and reducing the use of animals in vaccine testing, without compromising the scientific validity of the assay outcome.
Among the procedures we have developed or adapted to our work is ELISA, which we use to measure mouse antibodies to pertussis antigens and the Protective Antigen (PA) and Lethal Factor of Bacillus anthracis. ELISA is also used as part of the potency test of pertussis vaccines licensed in the US.
In addition, we have adapted an existing toxin neutralization assay (TNA) to measure anti-PA antibodies in mouse serum as part of an immunogenicity test aimed at refining an active protection test currently used to test the potency of anthrax vaccines, and are now validating this assay. The TNA uses macrophage-like cells as substrate.
We have also used Vero cells to measure the neutralizing activity of sera from mice and humans vaccinated with diphtheria toxoid. We have generated reference materials for anthrax and pertussis vaccines, including animal and human sera and monoclonal antibodies.
Biologicals 2013 Mar;41(2):111-4
Ability of ELISA and a toxin neutralization assay to detect changes in immunogenicity of a recombinant Bacillus anthracis protective antigen vaccine upon storage.
Domínguez-Castillo RI, Verma A, Amador-Molina JC, Sirota L, Arciniega JL
Infect Immun 2013 Jan;81(1):278-84
Use of site-directed mutagenesis to model the effects of spontaneous deamidation on the immunogenicity of Bacillus anthracis protective antigen.
Verma A, McNichol B, Domínguez-Castillo RI, Amador-Molina JC, Arciniega JL, Reiter K, Meade BD, Ngundi MM, Stibitz S, Burns DL
Dev Biol 2012;134:135-9
Potential application of the consistency approach for vaccine potency testing.
Arciniega J, Sirota LA
Procedia Vaccinol 2011;5(1):33-46
Improving animal welfare and reducing animal use for human vaccine potency testing: state of the science and future directions
Casey W, Schmitt M, McFarland R, Isbrucker R, Levis R, Arciniega J, Descamps J, Finn T, Hendriksen C, Horiuchi Y, Keller J, Kojima H, Sesardic D, Stickings P, Johnson NW, Lipscomb E, Allen D
Procedia Vaccinol 2011;5:47-59
Alternative methods and strategies to reduce, refine, and replace animal use for human vaccine post-licensing safety testing: state of the science and future directions
Isbrucker R, Levis R, Casey W, McFarland R, Schmitt M, Arciniega J, Descamps J, Finn T, Hendriksen C, Horiuchi Y, Keller J, Kojima H, Sesardic D, Stickings P, Johnson NW, Allen D
Biologicals 2011 Jul;39(4):236-41
Feasibility of the use of ELISA in an immunogenicity-based potency test of anthrax vaccines.
Jiménez-Alberto A, Parreiras P, Castelán-Vega J, Sirota L, Arciniega J
Clin Vaccine Immunol 2011 Feb;18(2):349-51
Reduction of immunogenicity of anthrax vaccines subjected to thermal stress, as measured by a toxin neutralization assay.
Castelan-Vega J, Corvette L, Sirota L, Arciniega J
J Mol Model 2010 Jul;16(7):1213-22
Homology modeling and molecular dynamics simulations of HgiDII methyltransferase in complex with DNA and S-adenosyl-methionine: Catalytic mechanism and interactions with DNA.
Castelán-Vega JA, Jiménez-Alberto A, Ribas-Aparicio RM
Vaccine 2009 Jul 16;27(33):4537-42
Comparability of ELISA and toxin neutralization to measure immunogenicity of Protective Antigen in mice, as part of a potency test for anthrax vaccines.
Parreiras PM, Sirota LA, Wagner LD, Menzies SL, Arciniega JL
Biologicals 2008 Jan;36(1):73-7
The consistency approach for the quality control of vaccines.
Hendriksen C, Arciniega JL, Bruckner L, Chevalier M, Coppens E, Descamps J, Duchêne M, Dusek DM, Halder M, Kreeftenberg H, Maes A, Redhead K, Ravetkar SD, Spieser JM, Swam H
Vaccine 2005 Mar 14;23(16):1993-9
Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants.
Berthold I, Pombo ML, Wagner L, Arciniega JL
Biologicals 2004 Sep;32(3):157-63
Validation of an anti-PA-ELISA for the potency testing of anthrax vaccine in mice.
Pombo M, Berthold I, Gingrich E, Jaramillo M, Leef M, Sirota L, Hsu H, Arciniega J