Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain

Autor: William J. Smith, Christine M. Taafe Gaunt, Lani Indrawati, Cecilia Giovarelli, Julie M. Skinner, Ivette Caro-Aguilar, Michael A. Winters, Robin M. Kaufhold, Denise K. Nawrocki, Jon H. Heinrichs, Yuhua Zhang
Rok vydání: 2016
Předmět:
0301 basic medicine
Serotype
T-Lymphocytes
CD1
Dose-Response Relationship
Immunologic
Drug Evaluation
Preclinical
Mice
Inbred Strains
Serogroup
Injections
Intramuscular
Pneumococcal conjugate vaccine
Pneumococcal Vaccines
03 medical and health sciences
Mice
0302 clinical medicine
Bacterial Proteins
Species Specificity
Conjugate vaccine
Medicine
Animals
Humans
030212 general & internal medicine
Mice
Inbred BALB C
Mice
Inbred C3H
Vaccines
Conjugate
General Veterinary
General Immunology and Microbiology
business.industry
Immunogenicity
Polysaccharides
Bacterial
Vaccination
Public Health
Environmental and Occupational Health
Antibody titer
Pneumonia
Pneumococcal
Virology
Antibodies
Bacterial
Disease Models
Animal
030104 developmental biology
Infectious Diseases
Streptococcus pneumoniae
Immunization
Pneumococcal vaccine
Immunoglobulin G
Immunology
Molecular Medicine
Female
business
Injections
Intraperitoneal
medicine.drug
Zdroj: Vaccine. 35(6)
ISSN: 1873-2518
Popis: Pneumococcal disease continues to be a medical need even with very effective vaccines on the market. Globally, there are extensive research efforts to improve serotype coverage with novel vaccines; therefore, conducting preclinical studies in different animal models becomes essential. The work presented herein focuses on evaluating a 15-valent pneumococcal conjugate vaccine (PCV15) in mice. Initially we evaluated several doses of PCV15 in Balb/c mice. The optimal vaccine dose was determined to be 0.4μg per pneumococcal polysaccharide (PS) (0.8μg of 6B) for subsequent studies. This PS dose was chosen for PCV evaluation in mice based on antibody levels determined by multiplexed electrochemiluminescent (ECL) assays, T-cell responses following in vitro stimulation with CRM197 peptides and protection from pneumococcal challenge. We then selected four mouse strains for evaluation: Balb/c, C3H/HeN, CD1 and Swiss Webster (SW), immunized with PCV15 by either intraperitoneal (IP) or intramuscular (IM) routes. We assessed IgG responses by ECL assays and functional antibody activity by multiplexed opsonophagocytic assays (MOPA). Every mouse strain evaluated responded to all 15 serotypes contained in the vaccine. Mice tended to have lower responses to serotypes 6B, 23F and 33F. The IP route of immunization resulted in higher antibody titers for most serotypes in Balb/c, C3H and SW. CD1 mice tended to respond similarly for most serotypes, regardless of route of immunization. Similar trends were observed with the four mouse strains when evaluating functional antibody activity. Given the differences in antibody responses based on mouse strain and route of immunization, it is critical to evaluate pneumococcal vaccines in multiple animal models to determine the optimal formulation before moving to clinical trials.
Databáze: OpenAIRE
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