Serum neutralizing antibody response to hepatitis A virus

Area of Science:

• Virology
• Immunology
• Hepatology

Background:

• Hepatitis A virus (HAV) causes significant liver disease globally.
• Assessing immunity to HAV is critical for vaccine development and public health.
• Understanding the kinetics of neutralizing antibody response is essential for evaluating protective immunity.

Purpose of the Study:

• To measure serum neutralizing antibody to HAV in experimentally infected primates and naturally infected humans.
• To correlate neutralizing antibody levels with viral replication, shedding, and clinical symptoms.
• To evaluate the utility of a novel assay for quantifying HAV neutralizing antibodies.

Main Methods:

• Development of an in vitro assay using autoradiographic detection of viral replication foci.
• Experimental infection of primates with HAV strains (PA-33, HM-175).
• Testing serum samples from primates and humans during a hepatitis A outbreak.

Main Results:

• HAV infection in primates elicited cross-neutralizing antibodies against different HAV strains.
• Neutralizing antibody levels correlated with immunoassay detection, appearing before liver enzyme elevation.
• A significant reduction in fecal viral antigen shedding was associated with neutralizing antibody presence.
• In humans, neutralizing antibodies were detected 3-5 days before symptom onset and found in 19S and 7S immunoglobulin fractions.

Conclusions:

• Neutralizing antibody is the primary mediator of immunity to HAV.
• The developed assay effectively quantifies HAV neutralizing antibodies.
• Quantification of neutralizing antibodies will aid in evaluating new HAV vaccines and understanding natural infection.