How to design effective vaccines: Lessons from an old success story

Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Expert Review of Vaccines (Impact Factor: 4.21). 06/2009; 8(5):543-6. DOI: 10.1586/erv.09.26
Source: PubMed


Evaluation of: Gaucher D, Therrien R, Kettaf N et al. Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J. Exp. Med. 205(13), 3119-3131 (2008). Despite the successful development of vaccines that are able to elicit potent and protective immune responses, the majority of vaccines were developed empirically and the mechanistic events leading to protective immune responses are often poorly understood. This impedes the development of new prophylactic as well as therapeutic vaccines for infectious diseases and cancer. Gaucher et al. took advantage of the effective yellow fever vaccine 17D to prospectively identify key immunological responses elicited by the vaccine using functional genomics and flow cytometric analysis. The results of the study clearly indicate 'that the immune response to a strong vaccine is preceded by the coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional and persistent immune response integrating all effector cells of the immune system'.

Download full-text


Available from: Stephen Gottschalk, Sep 28, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resumen Durante el siglo XIX las investigaciones en infectología y microbiología, confirmaron la teoría "contagionista" de la enfermedad, des-cartando la teoría miasmática, fomentando el desarrollo de técnicas para aislar los micro-organismos causantes de las infecciones y descubriendo los mecanismos de trasmisión de la enfermedad. Ante la dificultad de te-ner modelos animales para varios grupos de enfermedades, la experimentación en seres humanos se hizo necesaria, incluyendo la au-toinoculación de los investigadores. La historia de las investigaciones sobre la fiebre amarilla en Cuba es una experiencia paradigmática y fundamental de la salud pública y ejemplo del triunfo del plantea-miento de la infectología. Sin embargo, las circunstancias subyacentes a los triunfos científicos sobre la peste americana relatan una historia menos conocida, caracterizada
    Full-text · Article · Sep 2010 · Infectio
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The clinical outcome of the traditional adoptive cancer immunotherapy approaches involving the administration of donor-derived immune effectors, expanded ex vivo, has not met expectations. This could be attributed, in part, to the lack of sufficient high-avidity antitumor T-cell precursors in most cancer patients, poor immunogenicity of cancer cells, and the technological limitations to generate a sufficiently large number of tumor antigen-specific T cells. In addition, the host immune regulatory mechanisms and immune homeostasis mechanisms, such as activation-induced cell death (AICD), could further limit the clinical efficacy of the adoptively administered antitumor T cells. Since generation of a sufficiently large number of potent antitumor immune effectors for adoptive administration is critical for the clinical success of this approach, recent advances towards generating customized donor-specific antitumor-effector T cells by engrafting human peripheral blood-derived T cells with a tumor-associated antigen-specific transgenic T-cell receptor (TCR) are quite interesting. This manuscript provides a brief overview of the TCR engineering-based cancer immunotherapy approach, its advantages, and the current limitations.
    Preview · Article · Jan 2011 · The Scientific World Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the early immunologic events accompanying reactivated tuberculosis (TB) in HIV-infected individuals may yield insight into causes of reactivation and improve treatment modalities. We used the cynomolgus macaque (Macaca fascicularis) model of HIV-Mycobacterium tuberculosis coinfection to investigate the dynamics of multifunctional T cell responses and granuloma T cell phenotypes in reactivated TB. CD4(+) and CD8(+) T cells expressing Th1 cytokines (IFN-γ, IL-2, TNF) and Th2 cytokines (IL-4 and IL-10) were followed from latent M. tuberculosis infection to reactivation after coinfection with a pathogenic SIV. Coinfected animals experienced increased Th1 cytokine responses to M. tuberculosis Ags above the latent-response baseline 3-5 wk post-SIV infection that corresponded with peak plasma viremia. Th2 cytokine expression was not Ag specific, but strong, transient IL-4 expression was noted 4-7 wk post-SIV infection. Animals reactivating <17 wk post-SIV infection had significantly more multifunctional CD4(+) T cells 3-5 wk post-SIV infection and more Th2-polarized and fewer Th0-, Th1-polarized CD8(+) T cells during weeks 1-10 post-SIV infection than animals reactivating >26 wk post-SIV infection. Granuloma T cells included Th0-, Th1-, and Th2-polarized phenotypes but were particularly rich in cytolytic (CD107(+)) T cells. When combined with the changes in peripheral blood T cells, these factors indicate that events during acute HIV infection are likely to include distortions in proinflammatory and anti-inflammatory T cell responses within the granuloma that have significant effects on reactivation of latent TB. Moreover, it appears that mycobacteria-specific multifunctional T cells are better correlates of Ag load (i.e., disease status) than of protection.
    Full-text · Article · Feb 2011 · The Journal of Immunology
Show more