Principal Investigator

Nicholas J.
Mantis
Awardee Organization

Wadsworth Center
United States

Fiscal Year
2023
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

High-Throughput Dried Blood Spot (HT-DBS) Technologies in SARS COV-2 Serology and Vaccinology

As the COVID-19 pandemic continues to spread across the United States it is imperative that we implement technologies to screen large swaths of the population for the presence of antibodies to SARS-CoV-2. Serological surveillance not only affords a measure of virus exposure within a community at large but also provides information necessary to predict outbreak dynamics. Furthermore, as our understanding of how humoral factors contribute to controlling (and possibly exacerbating) COVID-19, it will be essential to have methods in place to measure the “quantity” and “quality” of antibodies associated with both natural SARS-CoV2 exposure and candidate SARS-CoV-2 vaccines. This U01 proposal seeks to advance the use of dried blood spots (DBS) in conjunction with a Luminex-based microsphere immunoassay (MIA) to enable high-throughput (HT) population-wide serological surveillance for SARS-CoV-2. Specifically, the proposal will expand the HTDBS assay to capture the breadth and complexity of SARS-CoV-2 antibody responses following natural infection, and develop a high-throughput competitive immunoassay (CIA) as a surrogate measure of SARSCoV-2 neutralizing antibody titers in DBS. The proposed platform technologies to be developed at the Wadsworth Center will contribute directly to NCI’s mission to “… develop, validate, improve and implement serological testing and associated technologies…” to address the COVID-19 pandemic.

Publications

  • Bajoria S, Kaur K, Kumru OS, Van Slyke G, Doering J, Novak H, Rodriguez Aponte SA, Dalvie NC, Naranjo CA, Johnston RS, Silverman JM, Kleanthous H, Love JC, Mantis NJ, Joshi SB, Volkin DB. Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants. Human vaccines & immunotherapeutics. 2022 Nov 30;18(5):2079346. Epub 2022 Jun 6. PMID: 35666264
  • Hempel H, Mantis N, Heaney CD, Pinto LA. The SeroNet Clinical and Translational Serology Task Force (CTTF) SARS-CoV-2 mucosal immunity methodological considerations and best practices workshop. Human vaccines & immunotherapeutics. 2023 Aug 1;19(2):2253598. PMID: 37695268
  • Bajoria S, Kumru OS, Doering J, Berman K, Slyke GV, Prigodich A, Rodriguez-Aponte SA, Kleanthous H, Love JC, Mantis NJ, Joshi SB, Volkin DB. Nanoalum Formulations Containing Aluminum Hydroxide and CpG 1018TM Adjuvants: The Effect on Stability and Immunogenicity of a Recombinant SARS-CoV-2 RBD Antigen. Vaccines. 2023 May 26;11. (6). PMID: 37376419
  • Czajka TF, Vance DJ, Mantis NJ. Slaying SARS-CoV-2 One (Single-domain) Antibody at a Time. Trends in microbiology. 2021 Mar;29(3):195-203. Epub 2020 Dec 16. PMID: 33446406
  • Yates JL, Ehrbar DJ, Hunt DT, Girardin RC, Dupuis AP 2nd, Payne AF, Sowizral M, Varney S, Kulas KE, Demarest VL, Howard KM, Carson K, Hales M, Ejemel M, Li Q, Wang Y, Peredo-Wende R, Ramani A, Singh G, Strle K, Mantis NJ, McDonough KA, Lee WT. Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity. Cell reports. Medicine. 2021 Jul 20;2(7):100329. Epub 2021 Jun 15. PMID: 34151306
  • Li Q, Humphries F, Girardin RC, Wallace A, Ejemel M, Amcheslavsky A, McMahon CT, Schiller ZA, Ma Z, Cruz J, Dupuis AP, Payne AF, Maryam A, Yilmaz NK, McDonough KA, Pierce BG, Schiffer CA, Kruse AC, Klempner MS, Cavacini LA, Fitzgerald KA, Wang Y. Mucosal nanobody IgA as inhalable and affordable prophylactic and therapeutic treatment against SARS-CoV-2 and emerging variants. Frontiers in immunology. 2022 Sep 12;13:995412. doi: 10.3389/fimmu.2022.995412. eCollection 2022. PMID: 36172366
  • Nemeth KL, Yauney E, Rock JM, Bievenue R, Parker MM, Styer LM. Use of Self-Collected Dried Blood Spots and a Multiplex Microsphere Immunoassay to Measure IgG Antibody Response to COVID-19 Vaccines. Microbiology spectrum. 2023 Feb 14;11(1):e0133622. Epub 2023 Jan 9. PMID: 36622204