Bukreyev Alexander, Belyakov Igor M
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007, USA.
Expert Rev Vaccines. 2002 Aug;1(2):233-45. doi: 10.1586/14760584.1.2.233.
Several obstacles exist for the development and use of live attenuated vaccines, including difficulty in achieving a proper balance between attenuation of viral replication and immunogenicity; inducing a strong T-helper 1 response in early life when the immune system is T helper 2 biased and immunization is sometimes associated with immunopathology and the immunosuppressive effect of maternal antibodies in infants. For some viral infections, the immune response to natural infection does not confer solid protection, complicating the task of vaccine development. The development of methods for generation of recombinant viruses provided new opportunities for improving the immunogenicity of live virus vaccine candidates, including the construction of viruses that express cytokines or other immunomodulating molecules. Depending on the choice of immunomodulating molecule, various stages of the immune response can be affected, such as antigen presentation or T-cell proliferation and differentiation. In addition to using the approach for development of viral live attenuated vaccines, it is currently being explored for the development of antitumor vaccines. For this type of vaccine, expression of tumor antigens and one or more immunomodulating molecules by one or several recombinant viruses has been proposed.
减毒活疫苗的研发和使用存在若干障碍，包括难以在病毒复制的减毒与免疫原性之间实现适当平衡；在免疫系统偏向于辅助性T细胞2的早期生命阶段诱导强烈的辅助性T细胞1反应，且免疫接种有时与免疫病理学以及婴儿体内母体抗体的免疫抑制作用相关。对于某些病毒感染，对自然感染的免疫反应并不能提供可靠的保护，这使疫苗研发工作变得复杂。重组病毒生成方法的发展为提高候选减毒活病毒疫苗的免疫原性提供了新机会，包括构建表达细胞因子或其他免疫调节分子的病毒。根据免疫调节分子的选择，免疫反应的各个阶段都可能受到影响，如抗原呈递或T细胞增殖与分化。除了将该方法用于减毒活病毒疫苗的研发外，目前也在探索将其用于抗肿瘤疫苗的研发。对于这类疫苗，有人提出由一种或几种重组病毒表达肿瘤抗原和一种或多种免疫调节分子。
