Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help.
Long-term antibody memory induced by synthetic peptide vaccination is protective against Streptococcus pyogenes infection and is independent of memory T cell help.
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DOI：
10.4049/jimmunol.1202333
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发表时间：
2013-03-15
期刊：
影响因子：
--
通讯作者：
Batzloff MR
中科院分区：
文献类型：
--
作者：
Pandey M;Wykes MN;Hartas J;Good MF;Batzloff MR
化脓性链球菌（A组链球菌；GAS）是一种与多种粘膜和全身感染相关的主要人类病原体。J8是一种从GAS的m蛋白衍生的保守区域合成肽，仅含有GAS的12个氨基酸，当与DT结合时，已被证明可以保护小鼠免受致命的GAS攻击。先前已证明这种保护是由抗体介导的。J8不含显性gas特异性t细胞表位。目前的研究检查了长期抗体记忆，并剖析了B细胞和t细胞的作用。我们的研究结果表明，疫苗接种产生特异性记忆b细胞和持久的抗体反应。记忆性b细胞反应可以在抗原或限制全细菌数量的刺激下被激活。我们进一步表明，这些记忆反应可以防止GAS的全身感染。激活记忆b细胞需要t细胞的帮助，但可以通过naïve t细胞在感染时直接响应GAS来提供帮助。因此，那些t细胞不能识别疫苗中短合成肽的个体将能够在感染时产生保护性和快速记忆抗体反应。这些研究大大加强了先前的发现，即J8-DT疫苗的保护作用是抗体介导的，并表明在为其他生物体设计疫苗时，t细胞帮助抗体反应的来源不必局限于生物体本身的序列。
Streptococcus pyogenes (group A streptococcus; GAS) is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Vaccination with J8, a conserved region synthetic peptide derived from the M-protein of GAS and containing only 12 amino acids from GAS, when conjugated to DT, has been shown to protect mice against a lethal GAS challenge. Protection has been previously shown to be antibody-mediated. J8 does not contain a dominant GAS-specific T-cell epitope. The current study examined long-term antibody memory and dissected the role of B and T-cells. Our results demonstrated that vaccination generates specific memory B-cells and long-lasting antibody responses. The memory B-cell response can be activated following boost with antigen or limiting numbers of whole bacteria. We further show that these memory responses protect against systemic infection with GAS. T-cell help is required for activation of memory B-cells but can be provided by naïve T-cells responding directly to GAS at the time of infection. Thus, individuals whose T-cells do not recognize the short synthetic peptide in the vaccine will be able to generate a protective and rapid memory antibody response at the time of infection. These studies significantly strengthen previous findings, which showed that protection by the J8-DT vaccine is antibody-mediated and suggest that in vaccine design for other organisms the source of T-cell help for antibody responses need not be limited to sequences from the organism itself.
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影响因子：
6.4
作者：
Batzloff, MR;Hayman, WA;Good, MF
通讯作者：
Good, MF
DOI：
10.1073/pnas.0903181106
发表时间：
2009-05-12
影响因子：
11.1
作者：
Galli, Grazia;Hancock, Kathy;Stephenson, Iain
通讯作者：
Stephenson, Iain
影响因子：
6.4
作者：
GORDON, DM;MCGOVERN, TW;BALLOU, WR
通讯作者：
BALLOU, WR
影响因子：
3.1
作者：
Harris, Aaron M.;Bhuiyan, M. Saruar;Harris, Jason B.
通讯作者：
Harris, Jason B.
DOI：
10.4049/jimmunol.1002955
发表时间：
2011-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
MacLeod MK;David A;McKee AS;Crawford F;Kappler JW;Marrack P
通讯作者：
Marrack P