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首页> 外文期刊>Vaccine >Balancing safety and immunogenicity in live-attenuated mycobacterial vaccines for use in humans at risk for HIV: Response to Misleading comments in Ranganathan et al. 'Recombinant pro-apoptotic Mycobacterium tuberculosis generates CD8+T cell responses against human immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice'
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Balancing safety and immunogenicity in live-attenuated mycobacterial vaccines for use in humans at risk for HIV: Response to Misleading comments in Ranganathan et al. 'Recombinant pro-apoptotic Mycobacterium tuberculosis generates CD8+T cell responses against human immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice'

机译:平衡减毒活疫苗中的安全性和免疫原性,以用于有艾滋病毒感染风险的人类:对Ranganathan等人的误导性评论的回应。 “重组促凋亡性结核分枝杆菌在新生小鼠中产生针对人类免疫缺陷病毒1型Env和结核分枝杆菌的CD8 + T细胞应答”

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We appreciate the comments of Kernodle et al. [1] concerning the limitations of various strategies to develop a safer and more immunogenic live-attenuated mycobacterial vaccine in response to our publication [2] U.D. Ranganathan, M.H. Larsen, J. Kim, S.A. Porcelli, W.R. Jacobs Jr. and G.J. Fennelly, Recombinant pro-apoptotic Mycobacterium tuberculosis generates CD8+ T cell responses against human immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice, Vaccine 28 (December (1)) (2009), pp. 152–161. Article | PDF (836 K) | View Record in Scopus | Cited By in Scopus (3)[2]. In particular, it has been difficult, as has been noted, to strike the “right balance between immunogenicity and attenuation” [3] in candidate auxotrophic mycobacterial strains so as to make them both sufficiently safe as well as effective. The safety of an improved live-attenuated mycobacterial vaccine is paramount considering that BCG causes disseminated disease at an annual rate of 0.42% following vaccination in infants with HIV infection [4]. In this context, it is important to note that the basis of reduced persistence in vivo of the 3dBCG vaccine (that contains deletions in secA2 and sigH, along with an allele for a dominant negative form of SodA), as pointed out by Sadagopal et al. [5] is in part a consequence of the stronger immune responses induced by this strain relative to the wild-type BCG parent strain [5]. Safety in SCID mice is generally considered a reliable first screen for safety in humans with immunosuppression [6].
机译:我们感谢Kernodle等人的评论。 [1]关于根据我们的出版物开发更安全,更具免疫原性的减毒活的分枝杆菌疫苗的各种策略的局限性[2]。 Ranganathan,M.H. Larsen,J.Kim,S.A. Porcelli,W.R. Jacobs Jr.和G.J.在新生小鼠中,重组促凋亡性结核分枝杆菌会针对人类免疫缺陷病毒1型Env和结核分枝杆菌产生CD8 + T细胞反应,疫苗28(12月(1))(2009年),第152-161页。文章PDF(836 K)|查看Scopus中的记录|在Scopus(3)[2]中被引用。特别是,正如已经指出的那样,很难在候选营养缺陷型分枝杆菌菌株中达到“免疫原性和减毒之间的正确平衡” [3],以使其既足够安全又有效。考虑到卡介苗在感染艾滋病毒的婴儿中接种后每年以0.42%的速度传播疾病,改良减毒活的分枝杆菌疫苗的安全性至关重要。[4]在此背景下,重要的是要注意,如Sadagopal等人指出的,3dBCG疫苗(在secA2和sigH中缺失,以及SodA显性阴性形式的等位基因等位基因)在体内持久性降低的基础。 。 [5]部分是由于该菌株相对于野生型BCG亲本菌株[5]诱导的更强的免疫反应的结果。 SCID小鼠的安全性通常被认为是对具有免疫抑制作用的人的安全性的可靠的初步筛选[6]。

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