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1. Vaccine targeting to mucosal lymphoid tissues promotes humoral immunity in the gastrointestinal tract.

Author

Kocabiyik O, Amlashi P, Vo AL, Suh H, Rodriguez-Aponte SA, Dalvie NC, Love JC, Andrabi R, and Irvine DJ

Subjects
Animals, Mice, Gastrointestinal Tract immunology, Lymphoid Tissue immunology, Immunity, Mucosal drug effects, SARS-CoV-2 immunology, COVID-19 prevention & control, COVID-19 immunology, Antibodies, Viral immunology, Lymph Nodes immunology, Immunoglobulin A immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Antibodies, Neutralizing immunology, Female, B-Lymphocytes immunology, Adjuvants, Vaccine, Mice, Inbred C57BL, Humans, Immunity, Humoral
Abstract

Viruses, bacteria, and parasites frequently cause infections in the gastrointestinal tract, but traditional vaccination strategies typically elicit little or no mucosal antibody responses. Here, we report a strategy to effectively concentrate immunogens and adjuvants in gut-draining lymph nodes (LNs) to induce gut-associated mucosal immunity. We prepared nanoemulsions (NEs) based on biodegradable oils commonly used as vaccine adjuvants, which encapsulated a potent Toll-like receptor agonist and displayed antigen conjugated to their surface. Following intraperitoneal administration, these NEs accumulated in gut-draining mesenteric LNs, priming strong germinal center responses and promoting B cell class switching to immunoglobulin A (IgA). Optimized NEs elicited 10- to 1000-fold higher antigen-specific IgG and IgA titers in the serum and feces, respectively, compared to free antigen mixed with NE, and strong neutralizing antibody titers against severe acute respiratory syndrome coronavirus 2. Thus, robust gut humoral immunity can be elicited by exploiting the unique lymphatic collection pathways of the gut with a lymph-targeting vaccine formulation.

Published
2024
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2. Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.

Author

Song G, Yuan M, Liu H, Capozzola T, Lin RN, Torres JL, He WT, Musharrafieh R, Dueker K, Zhou P, Callaghan S, Mishra N, Yong P, Anzanello F, Avillion G, Vo AL, Li X, Makhdoomi M, Feng Z, Zhu X, Peng L, Nemazee D, Safonova Y, Briney B, Ward AB, Burton DR, Wilson IA, and Andrabi R

Abstract

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites., Competing Interests: Declaration of interests G.S., W.H., P.Z., S.C., R.M., K.D., D.R.B. and R.A. are listed as inventors on pending patent applications describing the betacoronavirus broadly neutralizing antibodies. All other authors have no competing interests to declare.

Published
2023
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