Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations A Double-Blind, Placebo-controlled, Dose-Selection Trial

被引：83

作者：

Suliman, Sara ^{[1
,2
]}

Luabeya, Angelique Kany Kany ^{[1
,2
]}

Geldenhuys, Hennie ^{[1
,2
]}

Tameris, Michele ^{[1
,2
]}

Hoff, Soren T. ^{[3
]}

Shi, Zhongkai ^{[4
]}

Tait, Dereck ^{[5
]}

Kromann, Ingrid ^{[3
]}

Ruhwald, Morten ^{[3
]}

Rutkowski, Kathryn Tucker ^{[4
]}

Shepherd, Barbara ^{[4
]}

Hokey, David ^{[4
]}

Ginsberg, Ann M. ^{[4
]}

Hanekom, Willem A. ^{[1
,2
]}

Andersen, Peter ^{[3
]}

Scriba, Thomas J. ^{[1
,2
]}

Hatherill, Mark ^{[1
,2
]}

Oelofse, Rachel Elizabeth ^{[1
,2
]}

Stone, Lynnett ^{[1
,2
]}

Swarts, Anne Marie ^{[1
,2
]}

Onrust, Raida ^{[1
,2
]}

Jacobs, Gail ^{[1
,2
]}

Coetzee, Lorraine ^{[1
,2
]}

Khomba, Gloria ^{[1
,2
]}

Diamond, Bongani ^{[1
,2
]}

Companie, Alessandro ^{[1
,2
]}

Veldsman, Ashley ^{[1
,2
]}

Mulenga, Humphrey ^{[1
,2
]}

Cloete, Yolundi ^{[1
,2
]}

Steyn, Marcia ^{[1
,2
]}

Africa, Hadn ^{[1
,2
]}

Nkantsu, Lungisa ^{[1
,2
]}

Smit, Erica ^{[1
,2
]}

Botes, Janelle ^{[1
,2
]}

Bilek, Nicole ^{[1
,2
]}

Mabwe, Simbarashe ^{[1
,2
]}

机构：

[1] Univ Cape Town, South African TB Vaccine Initiat, Inst Infect Dis & Mol Med, Cape Town, South Africa

[2] Univ Cape Town, Div Immunol, Dept Pathol, Cape Town, South Africa

[3] Statens Serum Inst, Copenhagen, Denmark

[4] Aeras, Rockville, MD USA

[5] Aeras, Cape Town, South Africa

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2019年 / 199卷 / 02期

关键词：

tuberculosis; H56; subunit vaccine; QuantiFERON-TB (QFT); clinical trial; T-CELL RESPONSES; ACTIVE TUBERCULOSIS; BCG VACCINE; CD4; PROTECTION; INFECTION; H4IC31; ASSAY; MEMORY; ESAT-6;

D O I：

10.1164/rccm.201802-0366OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: Global tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium tuberculosis (M.tb). Objectives: We sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and M.tb-uninfected adults. Methods: We enrolled 98 healthy, HIV-uninfected, bacillus Calmette-Guerin-vaccinated, South African adults. M.tb infection was defined by QuantiFERON-TB (QFT) assay. QFT-negative participants received two vaccinations of different concentrations of H56 in 500 nmol of IC31 to enable dose selection for further vaccine development. Subsequently, QFT-positive and QFT-negative participants were randomized to receive two or three vaccinations to compare potential schedules. Participants were followed for safety and immunogenicity for 292 days. Measurements and Main Results: H56: IC31 showed acceptable reactogenicity profiles irrespective of dose, number of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse events were observed. The three H56 concentrations tested induced equivalent frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was only immunogenic in QFT-negative participants who received three vaccinations. Conclusions: Two or three H56:IC31 vaccinations at the lowest dose induced durable antigen-specific CD4 T-cell responses with acceptable safety and tolerability profiles in M.tb-infected and M.tb-uninfected adults. Additional studies should validate applicability of vaccine doses and regimens to both QFT-positive and QFT-negative individuals.

引用

页码：220 / 231

页数：12

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