Roeder, Alexa J.

Abstract Background While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of RNA vaccine recipients did not neutralize >50%. We termed this group “vaccine poor responders” (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs. Methods 269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines were evaluated. NAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose. Results Analysis of vaccine recipients revealed that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs showed an average 20-fold increase in NAb levels (range: 46%-99%). Conclusions The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission.

Abstract Background Coccidioidomycosis is often diagnosed with a collection of tests that measure a patient’s ability to mount an immune response to the fungus (antibody-based diagnostics) utilizing fungal protein preparations. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in diagnostic antigen preparations with potential for use in human serum. Methods An inhibition-based enzyme-linked immunoassay (ELISA) was developed that utilizes a monoclonal antibody specific for coccidioidal CTS1. CTS1 was quantified in commercial antigen preparations using recombinant CTS1 as a standard. Sera from 192 individuals from an endemic area were tested which included 78 patients (40.6%) with proven or probable coccidioidomycosis. Results The quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. Temporal constraints of availability of different lots of commercial antigens does not allow for immediate comparison of lot-to-lot variability. Assay results from patient serum samples correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Further analysis suggested that patient derived anti-CTS1 antibodies may overlap with the mouse monoclonal antibody used in the assay. This unexpected overlap in CTS1 binding suggests the assay can detect antigen, antibody, or both, which contributes to its high level of clinical sensitivity of 89.74% and specificity of 94.90%. Conclusions The CTS1 inhibition ELISA described in this report is a promising tool to aid in quality control of antigens used in the diagnosis of coccidioidomycosis. Further optimization is needed to harness its utility as a diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis.