Browsing by Author "Tong, Xin"

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    Humoral waning kinetics against SARS-CoV-2 is dictated by disease severity and vaccine platform
    (2024) Tong, Xin; Kellman, Benjamin; Avendaño Valenzuela, María José; Mendu, Maanasa; Hsiao, Jeff C.; Serrano García, Eileen Francisca; García Salum, Tamara Cristal; Muena, Nicolás; Pardo Roa, Catalina; Morales, Mauricio; Levicán Asenjo, Jorge Enrique; Salinas Ortiz, Erick David; Cárdenas-Cáceres, Simone; Riquelme Pérez, Arnoldo; Tischler, Nicole D.; Lauffenburger, Douglas A.; Alter, Galit; McNamara, Ryan P.; Medina, Rafael
    SARS-CoV-2 vaccine-acquired immunity provides robust cross-variant recognition, while infection-acquired immunity can be heterogenous, with disease severity often modulating post-recovery responses. We assessed antibody waning dynamics between infection- and vaccination-acquired immunity across variants of concern (VOC). mRNA vaccination induced potent, cross-VOC Spike recognition and functional responses, but waned more rapidly for Omicron Spike. Hospitalized individuals developed more durable functional responses with lower peaks compared to mRNA vaccination, while outpatients exhibited slower decay than inactivated vaccine recipients. Humoral decay for the receptor binding domain tracked with neutralizing antibody titers, while S2-directed responses tracked with antibody-dependent myeloid cellular phagocytosis. Boosting the recovered patients with mRNA or inactivated vaccines expanded humoral breadth, durability, and restored functional responses, eliminating the severity- and platform-associated decay differences. Therefore, post-recovery hybrid immunization compensates for this distinction and broadens humoral breadth, highlighting the value of boosting immunity in previously infected individuals.
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    Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines
    (2022) Bartsch, Yannic C.; Tong, Xin; Kang, Jaewon; Avendano, Maria Jose; Serrano, Eileen F.; Garcia-Salum, Tamara; Pardo-Roa, Catalina; Riquelme, Arnoldo; Cai, Yongfei; Renzi, Isabella; Stewart-Jones, Guillaume; Chen, Bing; Medina, Rafael A.; Alter, Galit
    The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fc gamma receptor (Fe gamma R) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific Fc gamma R2a and Fc gamma R3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to Fc gamma Rs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of Fc gamma R2a and Fc gamma R3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.