Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
Year: 2022
Type: article
Abstract: Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4 + and CD8 + T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4 + and CD8 + T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.
Source: Nature Communications
Authors: Julia T. Castro, Patrick Azevedo, Marcílio J. Fumagalli, Natalia S. Hojo-Souza, Natalia Salazar, Gregório G. Almeida, Livia I. Oliveira, Lídia Faustino, Lis R. Antonelli, Tomas G. Marçal, Marconi Augusto, Bruno Valiate, Alex Fiorini, Bruna Rattis, Simone G. Ramos, Mariela Piccin, Osvaldo Campos Nonato, Luciana Benevides, Rubens Magalhães, Bruno Cassaro, Gabriela Burle, Daniel Doro, Jorge Kalil, Edson Durigon, Andrés Salazar, Otávia Caballero, Helton Santiago, Alexandre Machado, João S. Silva, Flávio da Fonseca, Ana Paula Fernandes, Santuza R. Teixeira, Ricardo T. Gazzinelli
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: G1097860893, G1677423749, G2012850732, G396183989, G4993342397, G5850506195, G5960408532, G6244628984, G654803073, G6627412701, Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury, G7318746289, G7513797925, G8420762525
OpenAlex ID: W4292160658