Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON^®-TB Gold (+) Kenyan adults without evidence of tuberculosis

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• 作者：Douglas S. Walsh^a ; ¹ ; ^{douglas.walsh@va.gov" class="auth_mail" title="E-mail the corresponding author} ; Victorine Owira^a ; Mark Polhemus^a ; ³ ; Lucas Otieno^a ; Ben Andagalu^a ; Bernhards Ogutu^a ; John Waitumbi^a ; Anthony Hawkridge^d ; Barbara Shepherd^b ; Maria Grazia Pau^c ; Jerald Sadoff^c ; Macaya Douoguih^c ; J. Bruce McClain^b ; ² ; the Aeras C-012-402 Study Team⁴
• 关键词：Tuberculosis ; Vaccine ; AERAS-402 ; Safety ; Immunity ; Adenovirus-vectored
• 刊名：Vaccine
• 出版年：2016
• 出版时间：5 May 2016
• 年：2016
• 卷：34
• 期：21
• 页码：2430-2436
• 全文大小：555 K

文摘

In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON^®-TB Gold In-Tube test (QFT-G)(−) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(−) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(−) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects.