Browsing by Author "Pardo-Roa, C."

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    Is Gamma (P.1) Variant Associated with a Higher Severity in ICU Patients with SARS-CoV-2 Infection
    (2022) Vera, M.; Angulo, J.; Medina, R.; Ferres, M.; Bruhn, A.; Castro, R.; Pardo-Roa, C.
    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.
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    Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2023) Tong, X.; McNamara, R. P.; Avendano, M. J.; Serrano, E. F.; Garcia-Salum, T.; Pardo-Roa, C.; Bertera, H. L.; Chicz, T. M.; Levican, J.; Poblete, E.; Salinas, E.; Munoz, A.; Riquelme, A.; Alter, G.; Medina, R. A.
    Efficiency of SARS-CoV-2 vaccines has long been attributed to the neutralising capacity of the antibodies that are produced upon prime-boost vaccinations. Here authors show that upon vaccination with CoronaVac and BNT162b2 vaccines in prime-boost regimens, antibodies with Fc-effector functions to enhance cellular and innate immunity are also produced, albeit with different kinetics., Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.