Biomarkers and assessment of vaccine responses

Focus Technologies, Cypress, CA 90630, USA.
Biomarkers (Impact Factor: 2.26). 12/2005; 10 Suppl 1(s1):S50-7. DOI: 10.1080/13547500500216629
Source: PubMed


Vaccines for infectious diseases have in the past, and will into the future, relied on a variety of surrogate markers to monitor vaccine efficacy. The primary surrogate markers have been either the antibody titer to vaccine antigens or the measurement of antibody function such as anti-viral neutralizing activity. In recent years, the measurement of T-cell function in conjunction with or independent of antibody measurements have been used to assess vaccine efficacy. ELISPOT, flow cytometry and intra-cellular staining methods are used to determine the impact of vaccines on immune mediators such as interleukins, interferons, MHC expression and pro-inflammatory mediators. The relevant B-cell and T-cell surrogate markers for vaccine efficacy is dependent on the vaccine being used, so that no universal set of surrogate markers can be applied to all vaccines. The use of T-cell surrogate markers can be complicated by the lack of sensitivity to accurately measure intra-cellular mediators. Although typically this is not a problem for infectious disease vaccines, it is a major problem for cancer vaccines.

18 Reads
  • Source
    • "Can we define biomarkers for protection against tuberculosis that could help speed up clinical vaccine trials? Recent advances in global gene expression profiling using peripheral blood cells as surrogate tissue have led to the identification of biomarkers for predicting disease development, notably in cancer, or for monitoring drug activity (Anderson and LaBaer, 2005; Hogrefe, 2005). In principle, biomarkers can provide valuable insights into host defense against M. tuberculosis and as a result of vaccination. "
    [Show abstract] [Hide abstract]
    ABSTRACT: At the end of the 19th century, 40%–50% of all deaths in the working populations of major European cities were caused by tuberculosis (Kaufmann and Winau, 2005). It is no wonder that measures to reduce this burden were considered of high importance, not only for health but also for socioeconomic reasons. In this environment, Robert Koch embarked on elucidating the etiology of tuberculosis and other infectious diseases and laid the basis for the new discipline of medical microbiology by formulating the general conceptual framework and developing the necessary methodologies (Figure 1). Soon thereafter, Koch accidentally stumbled upon the yet-to-exist field of immunology during his attempt to develop a vaccine against tuberculosis. He had designed a subunit vaccine, which he claimed could cure tuberculosis. This claim was enthusiastically received all over the world (Figure 2). Yet, when this vaccine was tested in a clinical trial, it soon turned out to be Koch's greatest failure. Nevertheless, he continued to work on immune intervention for tuberculosis—in vain. In contrast, his sanitary and hygienic measures, which were based on the discovery of the infectious etiology of the disease, had a significant impact on tuberculosis control. Paul Ehrlich, Emil von Behring, the fathers of the concept of acquired specific immunity, were introduced to science through tuberculosis by Robert Koch. Similarly, the father of the concept of innate immunity, Elie Metchnikoff at the Pasteur Institute, had a genuine interest in tuberculosis. Undoubtedly, the importance of medical microbiology for society provided the bulk of the financial resources for the birth of immunology for Paul Ehrlich and Emil von Behring and Elie Metchnikoff. Yet, the relationship between immunology and tuberculosis has been ambivalent from the outset.
    Immunity 05/2006; 24(4):351-7. DOI:10.1016/j.immuni.2006.04.003 · 21.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunoassay (IA) technology has expanded the clinical utility of protein biomarkers, but demands for increased sensitivity, dynamic reporting ranges, and small sample volumes have limited the potential clinical usefulness of many biomarkers. We assessed the performance, including limits of detection (LODs) and the dynamic reporting range, of an IA-based technology, Erenna Immunoassay System, for a series of biomarkers, including cardiac troponin I (cTnI). Erenna IAs were used with 10 different and clinically important biomarkers to ascertain the LOD with various sample sizes (10 microL to 200 microL). The Erenna Immunoassay System generated LODs of 10-100 pg/L using 100 microL of sample. For cTnI, the LOD was 0.2 ng/L and a 10% CV was seen between 0.78 and 1.6 ng/L. The Erenna IA-based technology reproducibly measures protein biomarkers with detection limits of 10-100 pg/L, with a dynamic range of >4.5 logs in sample volumes of 50-150 microL.
    Clinical Chemistry 11/2007; 53(11):1990-5. DOI:10.1373/clinchem.2007.091181 · 7.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although mucosal responses are important for preventing infections with HIV, the optimal strategies for inducing them remain unclear. To evaluate vaccine strategies targeting the oral mucosal lymphoid tissue inductive sites as an approach to provide immunity at distal sites, we vaccinated healthy macaques via the palatine/lingual tonsils with aldrithiol 2 (AT-2) inactivated Simian immunodeficiency virus (SIV)mac239, combined with CpG-C immunostimulatory oligonucleotide (CpG-C ISS-ODN, C274) as the adjuvant. Macaques received 5 doses of C274 or control ODN C661 and AT-2 SIV on the tonsillar tissues every 6 weeks before being challenged rectally with SIVmac239, 8 weeks after the last immunization. Although no T-cell or B-cell responses were detected in the blood before challenge, antibody (Ab) responses were detected in the rectum. Immunization with AT-2 SIV significantly reduced the frequency of infection compared with nonimmunized controls, irrespective of adjuvant. In the vaccinated animals that became infected, peak viremias were somewhat reduced. SIV-specific responses were detected in the blood once animals became infected with no detectable differences between the differently immunized groups and the controls. This work provides evidence that vaccine immunogens applied to the oral mucosal associated lymphoid tissues can provide benefit against rectal challenge, a finding with important implications for mucosal vaccination strategies.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2009; 52(4):433-42. DOI:10.1097/QAI.0b013e3181b880f3 · 4.56 Impact Factor
Show more

Similar Publications

Preview (2 Sources)

18 Reads
Available from