Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

Autor: Christopher L. Cooper, Sina Bavari, Jesse T. Steffens, Sean A. Van Tongeren, Steven A. Kwilas, Karen A. Martins, Sarah L. Norris, Sabrina M. Stronsky, Jacqueline G. Benko
Rok vydání: 2016
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
PRR
pattern recognition receptor
medicine.medical_treatment
NAb
neutralizing antibody
Monophosphoryl Lipid A
lcsh:Medicine
MPLA
monophosphoryl lipid A
Antibodies
Viral
ELISA
Enzyme linked immunosorbent assay
ELISPOT
enzyme-linked immunospot assay
Ebola virus
0302 clinical medicine
T-Lymphocyte Subsets
BME
beta mercaptoethanol
Neutralizing antibody
PsVNA
pseudovirion neutralization assay
Adjuvant
Vaccines
lcsh:R5-920
ELISPOT
Immunogenicity
General Medicine
Ebolavirus
Adoptive Transfer
Vaccination
medicine.anatomical_structure
Pfu
plaque forming unit
Models
Animal
Cytokines
Female
IP
intraperitoneal
lcsh:Medicine (General)
Research Paper
TLR
Toll-like receptor
Durable protection
DSCF
Dwass
Steel
Critchlow-Fligner
T cell
CD
cluster of differentiation
Biology
IACUC
Institutional Animal Care and Use Committee
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
FBS
fetal bovine serum
PBS
phosphate buffered saline
Adjuvants
Immunologic
Immunity
medicine
IM
intramuscular
Animals
Ns
not significant
Lymphocyte Count
Vaccines
Virus-Like Particle
IQR
interquartile range
ma-EBOV
mouse-adapted Ebola virus
lcsh:R
FACS
fluorescence activated cell sorting
Hemorrhagic Fever
Ebola
Antibodies
Neutralizing
Virology
Disease Models
Animal
030104 developmental biology
Immunoglobulin G
USAMRIID
United States Army Medical Research Institute of Infectious Diseases
VLP
virus-like particle
Immunology
biology.protein
LN
lymph node
Immunization
GP
glycoprotein
Vaccine
Immune correlates
030215 immunology
Zdroj: EBioMedicine, Vol 3, Iss C, Pp 67-78 (2016)
EBioMedicine
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2015.11.041
Popis: Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.
Highlights • Adjuvants can prolong the protection afforded by protein-based vaccines and impact adaptive immune responses • Enhanced CD4 T cell responses, helper and effector, correlate with duration of protection • Durable protection from ma-EBOV is associated with Tfh frequency, Th1 antibody titers, and effector CD4 T cells Protein-based vaccines are extremely safe, but they sometimes require the addition of adjuvants to enhance immunogenicity. In this study, we compared the impact of multiple adjuvants on immunogenicity, focusing on the duration of vaccine-mediated protection in mice. We then looked at how each adjuvant impacted the immune response in order to identify correlates of that long lasting immunity. The most effective adjuvant/vaccine combinations elicited multifunctional CD4 T cell responses and a Th1-skewed antibody response. By transferring antigen-experienced CD4 T cells and serum into naïve animals, we demonstrated that both CD4 T cells and serum were critical for durable vaccine-mediated protection.
Databáze: OpenAIRE
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