Department of Pediatrics, Department of Pediatrics, Division of Infectious Diseases, University of Rochester Medical Center, Rochester, NY 14642, USA.
J Infect Dis. 2013 Jan 15;207(2):297-305. doi: 10.1093/infdis/jis684. Epub 2012 Nov 12.
The ability of influenza vaccines to elicit CD4(+) T cells and the relationship between induction of CD4(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination.
We tracked CD4(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins.
Our studies revealed that vaccination induced readily detectable CD4(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4(+) T cells was most tightly correlated with the antibody response.
These results indicate that CD4(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.
流感疫苗诱导 CD4(+) T 细胞的能力以及诱导 CD4(+) T 细胞与疫苗诱导中和抗体反应之间的关系一直存在争议。猪源 2009 年大流行性甲型 H1N1 流感病毒亚型（A[H1N1]pdm09）的出现为检查由新型和先前遇到的抗原组成的流感疫苗的反应提供了一个独特的机会，并探讨了疫苗接种后 B 细胞和 T 细胞反应之间的关系。
我们跟踪了接种单价亚单位 A(H1N1)pdm09 疫苗的人类受试者的 CD4(+) T 细胞和抗体反应。使用细胞因子酶联免疫斑点分析与代表不同流感病毒蛋白的肽池结合，评估 CD4(+) T 细胞反应的特异性和幅度。
我们的研究表明，接种疫苗可诱导针对血凝素（HA）和内部病毒蛋白保守部分的可检测到的 CD4(+) T 细胞。有趣的是，HA 特异性 CD4(+) T 细胞的扩增与抗体反应最密切相关。
这些结果表明，CD4(+) T 细胞的扩增可能是大流行性流感疫苗产生中和抗体反应的限制因素，并表明促进 CD4(+) T 细胞募集的方法可能会增加针对新型流感株的疫苗产生的中和抗体。
