Differential Multiplex Serology of vaccine-preventable diseases
Human pathogens are a major risk in public health and carry an enormous social-economic burden for all people. The lack of specific treatments for certain infectious diseases along with an increasing spread of antimicrobial and antiviral resistances highlights the potential global threat. Vaccination is one of the very few effective interventions to fight this challenge. Traditionally, clinical studies use conventional immunological biomarkers to measure the effectivity of a new or an established vaccine.
However, the picture on community level is very different, because measuring community effectiveness of a vaccination campaign encounters two methodological obstacles: Clinical features of most infections are not pathognomonic enough to allow syndromic measurements as indicator for one unique pathogen; existing immunological markers of vaccine preventable pathogens do not allow the distinction between immunological responses to natural infection from a responses induced by vaccination against the pathogen.
To address need for such a tool we are working on the development of assays, which are particularly needed in the context of: epidemics of pathogens with declining sporadic incidence; large vaccination campaigns in a phase of epidemiological transition; introduction of newly developed vaccines; vaccines of rather short termed effectivity due to seasonal variations of viral strains with differing antigenic characteristics, as typically know for influenza.
By far the most obvious and most ground-breaking impact of such a serological tool is to be expected for pathogens which are target of global elimination goals, such as measles, in order have a reproducible sero-epidemiological indicator for successful elimination.
As a proof of principle, we have developed a differential multiplex serology based on the Luminex® platform specific for the detection of human antibodies against Hepatitis A. With the proposed technology, we are able to distinguish between a hepatitis A vaccine-induced immune response and an immune response that originated from an infection with the hepatitis A wild type virus. A patent application at the European Patent Office is filed under the Application number: WO2016EP78554.
The basic technology and experiences gathered during the development of the differential multiplex serology for hepatitis A will be further exploited in order to expand the tool to other vaccine-preventable diseases to advance the understanding of vaccine effectivity in the context to infectious epidemiology.
Bohm K, Filomena A, Schneiderhan-Marra N, Krause G, Sievers C. Validation of HAV biomarker 2A for differential diagnostic of hepatitis A infected and vaccinated individuals using multiplex serology. Vaccine. 2017;35(43):5883-9. doi: 10.1016/j.vaccine.2017.08.089. PubMed PMID: 28919226.
Bohm K, Sievers C, Krause G (2015/2017) Method for differentiation of immune response in an individual. EP 3173789 A1.
HZI - Helmholtz-Zentrum für Infektionsforschung
DZIF - Deutsches Zentrum für Infektionsforschung
- Epidemiology- Prof. Dr. Gérard Krause