seronegativity

Seronegativity is the absence of detectable antibodies against a particular pathogen, antigen, or vaccine target in a person's serum, as determined by serologic testing. It can reflect no prior exposure, a very early infection before antibodies develop, or an inability to mount a detectable antibody response.

In infectious disease diagnostics, seronegativity can complicate interpretation. Antibody tests may be negative during the window period between exposure and seroconversion, or in infections that do not elicit a strong humoral response. In such cases, clinicians may rely on repeat serology, testing for other markers, or direct detection methods such as nucleic acid tests or antigen assays.

Seronegativity also applies to vaccination. Some individuals fail to generate detectable antibodies after vaccination (primary vaccine failure) or lose them over time (waning seroprotection). Assessment of immunity may include measuring antibody titers, though protection can persist via cellular or memory responses even when antibodies are not detectable. When seronegativity is suspected, revaccination or alternative regimens may be considered.

Causes of persistent seronegativity include immunodeficiency, immunosuppressive therapy, advanced age, genetic factors affecting antibody production, and limitations of assays such as sensitivity and specificity or preanalytic issues.

Seronegativity has important clinical and public health implications, influencing diagnosis, infection control, vaccination planning, and interpretation of seroprevalence studies.