PMID- 34025684
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20231111
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Identification, Selection and Immune Assessment of Liver Stage CD8 T Cell 
      Epitopes From Plasmodium falciparum.
PG  - 684116
LID - 10.3389/fimmu.2021.684116 [doi]
LID - 684116
AB  - Immunization with radiation-attenuated sporozoites (RAS) has been shown to 
      protect against malaria infection, primarily through CD8 T cell responses, but 
      protection is limited based on parasite strain. Therefore, while CD8 T cells are 
      an ideal effector population target for liver stage malaria vaccine development 
      strategies, such strategies must incorporate conserved epitopes that cover a 
      large range of class I human leukocyte antigen (HLA) supertypes to elicit 
      cross-strain immunity across the target population. This approach requires 
      identifying and characterizing a wide range of CD8 T cell epitopes for 
      incorporation into a vaccine such that coverage across a large range of class I 
      HLA alleles is attained. Accordingly, we devised an experimental framework to 
      identify CD8 T cell epitopes from novel and minimally characterized antigens 
      found at the pre-erythrocytic stage of parasite development. Through in silico 
      analysis we selected conserved P. falciparum proteins, using P. vivax orthologues 
      to establish stringent conservation parameters, predicted to have a high number 
      of T cell epitopes across a set of six class I HLA alleles representative of 
      major supertypes. Using the decision framework, five proteins were selected based 
      on the density and number of predicted epitopes. Selected epitopes were 
      synthesized as peptides and evaluated for binding to the class I HLA alleles in 
      vitro to verify in silico binding predictions, and subsequently for stimulation 
      of human T cells using the Modular IMmune In-vitro Construct (MIMIC((R))) 
      technology to verify immunogenicity. By combining the in silico tools with the ex 
      vivo high throughput MIMIC platform, we identified 15 novel CD8 T cell epitopes 
      capable of stimulating an immune response in alleles across the class I HLA 
      panel. We recommend these epitopes should be evaluated in appropriate in vivo 
      humanized immune system models to determine their protective efficacy for 
      potential inclusion in future vaccines.
CI  - Copyright (c) 2021 Tucker, Schanen, Phares, Sassano, Terry, Hindocha, Moise, 
      Kotraiah, Martin, De Groot, Drake, Gutierrez and Noe.
FAU - Tucker, Kenneth D
AU  - Tucker KD
AD  - Leidos Life Sciences, Leidos Inc., Frederick, MD, United States.
FAU - Schanen, Brian C
AU  - Schanen BC
AD  - Sanofi Pasteur, Orlando, FL, United States.
FAU - Phares, Timothy W
AU  - Phares TW
AD  - Leidos Life Sciences, Leidos Inc., Frederick, MD, United States.
FAU - Sassano, Emily
AU  - Sassano E
AD  - Sanofi Pasteur, Orlando, FL, United States.
FAU - Terry, Frances E
AU  - Terry FE
AD  - EpiVax Inc., Providence, RI, United States.
FAU - Hindocha, Pooja
AU  - Hindocha P
AD  - EpiVax Inc., Providence, RI, United States.
FAU - Moise, Leonard
AU  - Moise L
AD  - EpiVax Inc., Providence, RI, United States.
FAU - Kotraiah, Vinayaka
AU  - Kotraiah V
AD  - Leidos Life Sciences, Leidos Inc., Frederick, MD, United States.
FAU - Martin, William D
AU  - Martin WD
AD  - EpiVax Inc., Providence, RI, United States.
FAU - De Groot, Anne S
AU  - De Groot AS
AD  - EpiVax Inc., Providence, RI, United States.
AD  - University of Georgia Center for Vaccines and Immunology, Athens, GA, United 
      States.
FAU - Drake, Donald R 3rd
AU  - Drake DR 3rd
AD  - Sanofi Pasteur, Orlando, FL, United States.
FAU - Gutierrez, Gabriel M
AU  - Gutierrez GM
AD  - Leidos Life Sciences, Leidos Inc., Frederick, MD, United States.
FAU - Noe, Amy R
AU  - Noe AR
AD  - Leidos Life Sciences, Leidos Inc., Frederick, MD, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210507
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Malaria Vaccines)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Computer Simulation
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Human Experimentation
MH  - Humans
MH  - Liver/*parasitology
MH  - Malaria Vaccines/genetics/immunology
MH  - Plasmodium falciparum/genetics/*immunology
PMC - PMC8138313
OTO - NOTNLM
OT  - CSP
OT  - MIMIC
OT  - SPECT-2
OT  - epitopes
OT  - malaria
OT  - vaccine
COIS- AN, TP, KT, VK, and GG are employees of Leidos, Inc., the prime contractor for 
      Malaria Vaccine Development Program (MVDP) Contract AID-OAA-C-15-00071. FT, LM, 
      WM, and AG are employees of EpiVax, Inc., an MVDP subcontractor. BS, ES, and DD 
      are employees of Sanofi Pasteur, an MVDP subcontractor. BS, DD, and ES hold 
      Sanofi shares and/or stock options. PH was a previous employee of EpiVax, Inc. 
      The remaining authors declare that the research was conducted in the absence of 
      any commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/25 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/01/01
CRDT- 2021/05/24 08:04
PHST- 2021/03/22 00:00 [received]
PHST- 2021/04/13 00:00 [accepted]
PHST- 2021/05/24 08:04 [entrez]
PHST- 2021/05/25 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.684116 [doi]
PST - epublish
SO  - Front Immunol. 2021 May 7;12:684116. doi: 10.3389/fimmu.2021.684116. eCollection 
      2021.