Neutralizing antibody response to SARS-CoV-2 variants, as determined by the MSD multiplex assay, following COVID-19 vaccination in cancer patients.

Background: Immunocompromised populations, especially cancer patients, rely on the effectiveness of the COVID-19 vaccines to protect against severe infection or death, both against the original wild-type (WT) SARS CoV-2 virus and its many variants that have emerged. Methods: We conducted a study using serum samples from cancer patients who received the original mRNA-1273 COVID-19 vaccine. The Meso Scale Discovery (MSD) multiplex assay was used to assess angiotensin-converting enzyme 2 (ACE2) binding inhibition as a surrogate in this population for neutralization response against the WT SARS-CoV-2 receptor binding domain (RBD) antigen, along with nine of its variants. Confidence intervals were used to compare results between timepoints, and Spearman correlation coefficients were used to compare the results between antigen variants. Results: A positive correlation was found between the binding inhibition and previously reported neutralizing antibody titers against the WT antigen. All 168 participants showed an increase in binding inhibition following the third vaccine dose against each variant tested, however there was no significant difference in binding inhibition between variants. Positive correlations were also found between binding inhibition and previously reported total antibody titers against the WT antigen at each timepoint. Highest binding inhibitions were to the WT, New York, and Alpha variants, while the lowest were to the Beta and Gamma variants. Conclusions: Original vaccines against SARS-CoV-2 are immunogenic against the WT virus and many of its variants, even in immunocompromised populations such as cancer patients. Use of the MSD multiplex assay may be an alternative to viral neutralization assays depending on the subject population characteristics.