Role of Targeted Proteomics in Antibody Response

In order to determine variant-specific SARS-CoV-2 antibody response, quantitative, multiplexed, and specific target proteomics were used

FREMONT CA: The world’s fastest and largest worldwide immunization campaigns were developed and implemented due to the introduction of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses. However, the loss of immunity over time, as well as the introduction of many SARS-CoV-2 variants of concern (VOCs), underscores the need for more accurate testing to assess the need for and timing of booster vaccinations. Although first-generation tests were widely used, it was discovered that they overestimated the true protective immunity against VOCs. Current neutralizing antibody (NAb) measurement technologies have been proven to have low clinical value. In contrast, serological approaches (ELISA or ECLIA) have been found to quantify only a portion of the antibody response.

A new study published in the pre-print server medRxiv* developed a "bait and capture" system, followed by multiplexed and targeted proteomic liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses for comparing immune correlates in response to vaccination, natural infection, and protection against VOCs.

The present research included serum samples from the COVIDsortium study, which had already undergone longitudinal immunological examination.Twenty-five healthcare workers (HCWs) with previous laboratory evidence of wild-type SARS-CoV-2 infection and twenty-six HCWs with no SARS-CoV-2 infection participated in the study. After that, an immunocomplex assay for SARS-CoV-2 was performed, followed by immunocomplex protein digestion.

Immunoglobulins IgG1, 2, 3 & 4, IgA1, IgM, and complement factors C1q, C4b, and C9 were found in serum samples from SARS-CoV-2 positive HCWs. Except for the Beta version, increasing exposure to SARS-CoV-2 VOCs increased the immunocomplex. As a result, the current study was able to show antibody responses in non-hospitalized healthcare workers three weeks after immunization. The LC-MS/MS multiplex assay was developed to be easily converted into clinical laboratory settings, even though it is a research standard assay. To gain a better understanding of the changing antibody-mediated immune response to SARS-CoV-2, more research is needed to evaluate the influence of antibody response over time, the severity of infection from different variations, and the change in immunocomplex with age.