Centre for Clinical Vaccinology and Tropical Medicine, Oxford University, Churchill Hospital, Oxford, UK.
Vaccine. 2009 Dec 10;28(1):21-7. doi: 10.1016/j.vaccine.2009.09.132. Epub 2009 Oct 17.
Vaccination with viral-based vaccines continues to hold promise for the prevention of malaria. Whilst antigen-specific T cell responses are considered a major aim of such an approach, a role for induced NK cells as anti-malarial effector cells, or in shaping T cell responses, has received less attention. In this study naïve human volunteers were vaccinated in a prime-boost vaccination regimen comprising recombinant viral vectors fowlpox (FP9) and modified vaccinia Ankara (MVA) encoding liver-stage antigens, or a virosome vaccine. Significant T cell responses specific for the vectored vaccine antigens were demonstrated by IFNgamma ELISPOT and intracellular cytokine staining (ICS) for IFNgamma and IL-2, the ICS being associated with increased time to parasitaemia following subsequent challenge. Numbers of CD56(bright) lymphocytes increased significantly following vaccination, as did CD3(+) CD56(+) lymphocytes, whilst CD56(dim) cells did not. No such increases were seen with the virosome vaccine. There was no significant correlation of these CD56(+) populations with the antigen-specific T cell responses nor time to parasitaemia. To investigate pathways of immune activation that could contribute to these lymphocyte responses, viral vectors were shown in vitro to efficiently infect APCs but not lymphocytes, and stimulated inflammatory cytokines such as type I interferons. In conclusion, measuring antigen-specific T cells is more meaningful than NK cells in these vaccination regimens.
基于病毒的疫苗接种在预防疟疾方面仍然具有很大的潜力。虽然抗原特异性 T 细胞反应被认为是这种方法的主要目标，但诱导的 NK 细胞作为抗疟效应细胞，或在塑造 T 细胞反应方面的作用，受到的关注较少。在这项研究中，将 naive 人类志愿者用包含编码肝期抗原的重组病毒载体禽痘病毒（FP9）和改良安卡拉痘苗（MVA）的初免-加强疫苗方案，或病毒体疫苗进行接种。通过 IFNγ ELISPOT 和 IFNγ 和 IL-2 的细胞内细胞因子染色（ICS），证明了针对载体疫苗抗原的显著 T 细胞反应，ICS 与随后的寄生虫血症挑战后寄生虫血症时间的增加相关。接种后 CD56（明亮）淋巴细胞数量显著增加，CD3（+）CD56（+）淋巴细胞数量也增加，而 CD56（暗淡）细胞没有增加。病毒体疫苗没有观察到这种增加。这些 CD56（+）群体与抗原特异性 T 细胞反应或寄生虫血症时间没有显著相关性。为了研究可能有助于这些淋巴细胞反应的免疫激活途径，研究表明，病毒载体在体外可以有效地感染 APC 但不能感染淋巴细胞，并刺激炎症细胞因子，如 I 型干扰素。总之，在这些疫苗接种方案中，测量抗原特异性 T 细胞比 NK 细胞更有意义。
