Modelling the relationship between antibody-dependent enhancement and immunological distance with application to...

Area of Science:

• Epidemiology
• Immunology
• Mathematical Modeling

Background:

• Antibody-dependent enhancement (ADE) is a phenomenon where antibodies against one pathogen can enhance infection by immunologically similar pathogens.
• Secondary dengue virus infections are a significant risk factor for severe dengue hemorrhagic fever (DHF).
• It is hypothesized that ADE contributes to the immunological distance observed between the four dengue virus serotypes.

Purpose of the Study:

• To investigate the hypothesis that antibody-dependent enhancement (ADE) is responsible for the immunological distance between dengue virus serotypes.
• To analyze the impact of different forms of cross-enhancement (susceptibility, transmission, mortality) on dengue virus dynamics and serotype coexistence.

Main Methods:

• Development and analysis of an epidemic model for dengue.
• Separate modeling of immunological distance and immune cross-reaction strength.
• Inclusion of three forms of cross-enhancement: affecting susceptibility, transmission, and mortality.

Main Results:

• Susceptibility and transmission enhancement can lead to periodicity or chaos, confirming previous findings, but mortality enhancement does not.
• No form of enhancement leads to competitive exclusion when dengue virus strains have identical basic reproductive numbers.
• Susceptibility or transmission enhancement allows greater immunological similarity between coexisting strains, while mortality enhancement promotes greater distinction.

Conclusions:

• All three forms of enhancement (susceptibility, transmission, mortality) are potentially associated with DHF.
• Mortality enhancement must be the dominant form if ADE is indeed responsible for the immunological distance between dengue serotypes.
• The findings provide insights into dengue virus evolution and the pathogenesis of DHF.