Biomarkers and assessment of vaccine responses
WAYNE R. HOGREFE
Focus Technologies, Cypress, CA, USA
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.
Keywords: Vaccine response, ELISPOT, tetramer
The term ‘biomarkers’ covers a multitude of chemical and biological molecules in a
wide range of pathologic conditions including infectious disease, cardiovascular
disease, neurological diseases, inflammatory diseases and many more. Recently, the
term biomarker has been defined as biomolecules such as mRNA, proteins, peptides
and small molecules, that can be quantitated, predict disease or drug activity and
are ‘novel’ (Diller 2004). ‘Novel’ in this definition means the biomarker is neither
an established diagnostic marker nor a surrogate marker used to predict clinical
endpoints. With such a strict definition, no markers used in infectious disease and
cancer vaccine development would qualify as a ‘biomarker’, since the only vaccine
markers available are surrogate markers measuring various components of the
immune system. Therefore, this review is limited to surrogate markers of the immune
response to both infectious disease and cancer vaccines.
Biomarkers are utilized at two stages of vaccine development. The first stage is to
identify appropriate immunogens where the measurement of end-stage immune
function such as antibody levels is utilized. The second stage is to establish vaccine
efficacy as well as assess protection of the proposed vaccine (Krause 1998). Both
humoral and cell-mediated immunity biomarkers are used in this stage. Immune
response biomarkers that correlate with protection are used to determine efficacy
Correspondence: Wayne R. Hogrefe, 5785 Corporate Avenue, Cypress, CA 90630, USA. Tel: 714-220-
1900. Fax: 714-821-3364. Email: firstname.lastname@example.org
ISSN 1354-750X print/ISSN 1366-5804 online # 2005 Taylor & Francis
Biomarkers, November 2005; 10(Supplement 1): S50?/S57
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Biomarkers and assessment of vaccine responses