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Discover how PEPperPRINT Peptide Microarray products have been used in different fields of research.

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Non-Neutralizing Antibody Functions Predict Susceptibility to SARS-CoV-2 Infection after mRNA Booster Vaccination

Levy, Shlomia; Trifkovic, Sanja; Mielke, Dieter; Oppenheimer, Hannah; Goodman, Derrick; Ostrovsky, Daniel; Sanfield-Oakley, Sherry A.; Brackett, Caroline; Friedman, Lilach M; Kerkau, Melissa; Webby, Richard; Tomaras, Georgia; Guido, Ferrari; Nesher, Lior; Hertz, Tomer
Jan 2026
10.2139/ssrn.6019238
Previous studies have shown that neutralizing and binding antibody titers are correlates of protection for symptomatic SARS-CoV-2 infection. We previously reported that individuals with low IgG and IgA baseline immune history (BIH) to SARS-CoV-2 variants were at increased risk of symptomatic infection in study of healthcare workers that received 3 or 4 doses of the Pfizer BNT-1262b2 vaccine. We also found that 1-month post-vaccination with the 4th booster dose, individuals with low-BIH mounted significant rises in binding and neutralizing antibody titers, to levels comparable to those of individuals with high-BIH, demonstrating that their increased risk was not due to inability to respond to vaccination. To further study the underlying factors that are associated with increased risk, we conducted a systems serology study of 40 low-BIH and 40 high-BIH individuals across 7 months of follow-up. We found that individuals with low BIH exhibited a significantly higher risk of symptomatic infection (HR=2.691, p=0.0065) and mounted weaker IgA and antibody-dependent cellular cytotoxicity (ADCC) responses compared to high-BIH individuals, particularly against Omicron and Delta variants. Baseline levels of the chemokine CXCL-11 were elevated in the low-BIH group. We then showed that baseline immune profiles can be used to train a prediction model of infection risk across 7 months of follow-up with 76% accuracy. IgA, ADCC and ADCP baseline features were dominant predictors of susceptibility. Our findings suggest that non-neutralizing antibody functions, especially IgA and ADCC, contribute to protection against symptomatic SARS-CoV-2 infection and that serology-guided stratification can enhance discovery of immune correlates of risk informing future vaccine design and deployment strategies.

Anti-COX-2 Autoantibody is a Novel Marker of Immune Aplastic Anemia

Kelkka, Tiina; Tyster, Mikko; Lundgren, Sofie; Feng, Xingmin; Kerr, Cassandra; Hosokawa, Kohei; Huuhtanen, Jani; Keränen, Mikko; Kawakami, Toru; Patel, Bhavisha; Maeda, Yuka; Nieminen, Otso; Kasanen, Tiina; Aronen, Pasi; Yadav, Bhagwan; Rajala, Hanna; Nakazawa, Hideyuki; Jaatinen, Taina; Hellstrom-Lindberg, Eva; Ogawa, Seishi; Ishida, Fumihiro; Nishikawa, Hiroyoshi; Nakao, Shinji; Maciejewski, Jaroslaw; Young, Neal S.; Mustjoki, Satu
May 2022
10.21203/rs.3.rs-1653776/v1
In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing > 9 000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclo-oxygenase 2 (COX-2, aCOX-2 Ab). 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the > 40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable diagnostic tool.

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome

Fathi, Anahita; Dahlke, Christine; Krähling, Verena; Kupke, Alexandra; Okba, Nisreen M. A.; Raadsen, Matthijs P.; Heidepriem, Jasmin; Müller, Marcel A.; Paris, Grigori; Lassen, Susan; Klüver, Michael; Volz, Asisa; Koch, Till; Ly, My L.; Friedrich, Monika; Fux, Robert; Tscherne, Alina; Kalodimou, Georgia; Schmiedel, Stefan; Corman, Victor M.; Hesterkamp, Thomas; Drosten, Christian; Loeffler, Felix F.; Haagmans, Bart L.; Sutter, Gerd; Becker, Stephan; Addo, Marylyn M.
Feb 2022
10.1101/2022.02.14.22270168
Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials.

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