Protective CD8(+) T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation
Author(s)
Type
Journal Article
Abstract
Induction of antigen-specific CD8 þ T cells offers the prospect of immunization against many
infectious diseases, but no subunit vaccine has induced CD8 þ T cells that correlate with
efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus
vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency
T-cell responses (median 42400 SFC/106 peripheral blood mononuclear cells) to
the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective
efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays
time to patency through substantial reduction of liver-stage parasite burden in five more
(5/14, 36%), P ¼ 0.008 compared with controls. The frequency of monofunctional interferon-g-producing
CD8 þ T cells, but not antibodies, correlates with sterile protection
and delay in time to patency (Pcorrected ¼ 0.005). Vaccine-induced CD8 þ T cells provide
protection against human malaria, suggesting that a major limitation of previous vaccination
approaches has been the insufficient magnitude of induced T cells.
infectious diseases, but no subunit vaccine has induced CD8 þ T cells that correlate with
efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus
vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency
T-cell responses (median 42400 SFC/106 peripheral blood mononuclear cells) to
the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective
efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays
time to patency through substantial reduction of liver-stage parasite burden in five more
(5/14, 36%), P ¼ 0.008 compared with controls. The frequency of monofunctional interferon-g-producing
CD8 þ T cells, but not antibodies, correlates with sterile protection
and delay in time to patency (Pcorrected ¼ 0.005). Vaccine-induced CD8 þ T cells provide
protection against human malaria, suggesting that a major limitation of previous vaccination
approaches has been the insufficient magnitude of induced T cells.
Date Issued
2013-11-28
Date Acceptance
2013-10-29
Citation
Nature Communications, 2013, 4
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
4
Copyright Statement
© The Authors 2013. This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
VACCINIA VIRUS ANKARA
POLYMERASE-CHAIN-REACTION
PRIME-BOOST IMMUNIZATION
PHASE 2A TRIAL
NAIVE ADULTS
MEDIATED PROTECTION
NONHUMAN-PRIMATES
INFLUENZA-VIRUS
RHESUS-MONKEYS
DNA VACCINES
Adenoviruses, Simian
Adolescent
Adult
Animals
Antibodies, Protozoan
CD8-Positive T-Lymphocytes
Female
Genetic Vectors
Humans
Immunity, Cellular
Immunization
Immunization, Secondary
Interferon-gamma
Leukocytes, Mononuclear
Malaria Vaccines
Malaria, Falciparum
Male
Middle Aged
Plasmodium falciparum
Protozoan Proteins
Vaccinia virus
Young Adult
MD Multidisciplinary
Publication Status
Published
Article Number
2836