Cryopreservation-related loss of antigen-specific IFNγ producing CD4 + T-cells can skew immunogenicity data in vaccine trials: Lessons from a malaria vaccine trial substudy

Autor: Katie J. Ewer, Tom Ford, Jill Gilmour, Nicola Winstone, Len Dally, Claire Wenden, Josephine H. Cox, Alison Mbekeani, Merribeth Morin, Adrian V. S. Hill
Přispěvatelé: Bill & Melinda Gates Foundation, PATH
Rok vydání: 2017
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Enzyme-Linked Immunospot Assay
MULTICENTER
Drug Evaluation
Preclinical
Research & Experimental Medicine
BLOOD MONONUCLEAR-CELLS
TRAP
0302 clinical medicine
INFECTION
PROGRAM
IMMUNE-RESPONSES
Malaria vaccine
ELISPOT
Immunogenicity
11 Medical And Health Sciences
MVA
Flow Cytometry
3. Good health
medicine.anatomical_structure
Infectious Diseases
Medicine
Research & Experimental
Molecular Medicine
Life Sciences & Biomedicine
CLINICAL-TRIALS
T cell
Immunology
EFFECTOR
ChAd63
Biology
Article
Specimen Handling
Interferon-gamma
03 medical and health sciences
Clinical Trials
Phase II as Topic
CSP
Virology
Immunology and Microbiology(all)
Malaria Vaccines
medicine
Humans
ASSAYS
Cryopreservation
Science & Technology
Staining and Labeling
General Veterinary
General Immunology and Microbiology
MEMORY
PBMC
Vaccine trial
Public Health
Environmental and Occupational Health
06 Biological Sciences
medicine.disease
veterinary(all)
Malaria
Clinical trial
030104 developmental biology
HIV/AIDS VACCINE
07 Agricultural And Veterinary Sciences
CD8
030215 immunology
Zdroj: Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2017.02.038
Popis: Ex vivo functional immunoassays such as ELISpot and intracellular cytokine staining (ICS) by flow cytometry are crucial tools in vaccine development both in the identification of novel immunogenic targets and in the immunological assessment of samples from clinical trials. Cryopreservation and subsequent thawing of PBMCs via validated processes has become a mainstay of clinical trials due to processing restrictions inherent in the disparate location and capacity of trial centres, and also in the need to standardize biological assays at central testing facilities. Logistical and financial requirement to batch process samples from multiple study timepoints are also key. We used ELISpot and ICS assays to assess antigen-specific immunogenicity in blood samples taken from subjects enrolled in a phase II malaria heterologous prime-boost vaccine trial and showed that the freeze thaw process can result in a 3 to 5-fold reduction of malaria antigen-specific IFNγ-producing CD3+CD4+ effector populations from PBMC samples taken post vaccination. We have also demonstrated that peptide responsive CD8+ T cells are relatively unaffected, as well as CD4+ T cell populations that do not produce IFNγ. These findings contribute to a growing body of data that could be consolidated and synthesised as guidelines for clinical trials with the aim of increasing the efficiency of vaccine development pipelines.
Databáze: OpenAIRE
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