Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins

Immunity ◽  
2021 ◽  
Author(s):  
Fang Chen ◽  
Netanel Tzarum ◽  
Xiaohe Lin ◽  
Erick Giang ◽  
Rodrigo Velázquez-Moctezuma ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nanda Kishore Routhu ◽  
Narayanaiah Cheedarla ◽  
Venkata Satish Bollimpelli ◽  
Sailaja Gangadhara ◽  
Venkata Viswanadh Edara ◽  
...  

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.


1992 ◽  
Vol 8 (6) ◽  
pp. 1117-1123 ◽  
Author(s):  
JORGE RONCO ◽  
JEAN-FRANCOIS DEDIEU ◽  
FRANCOIS-NOËL MARIE ◽  
ABRAHAM PINTER ◽  
MICHEL KACZOREK ◽  
...  

Virology ◽  
2005 ◽  
Vol 331 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Christoph Grundner ◽  
Yuxing Li ◽  
Mark Louder ◽  
John Mascola ◽  
Xinzhen Yang ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0172524 ◽  
Author(s):  
Juan Pablo Jaworski ◽  
Peter Bryk ◽  
Zachary Brower ◽  
Bo Zheng ◽  
Ann J. Hessell ◽  
...  

2000 ◽  
Vol 74 (6) ◽  
pp. 2960-2965 ◽  
Author(s):  
Ilnour Ourmanov ◽  
Miroslawa Bilska ◽  
Vanessa M. Hirsch ◽  
David C. Montefiori

ABSTRACT Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene products (MVA-SIV). Animals received either MVA-gag-pol, MVA-env, MVA-gag-pol-env, or nonrecombinant MVA. Although no animals were completely protected from infection with SIV, animals immunized with recombinant MVA-SIV vaccines had lower virus loads and prolonged survival relative to control animals that received nonrecombinant MVA (I. Ourmanov et al., J. Virol. 74:2740–2751, 2000). Titers of neutralizing antibodies measured with the vaccine strain SIVsmH-4 were low in the MVA-env and MVA-gag-pol-env groups of animals and were undetectable in the MVA-gag-pol and nonrecombinant MVA groups of animals on the day of challenge (4 weeks after final immunization). Titers of SIVsmH-4-neutralizing antibodies remained unchanged 1 week later but increased approximately 100-fold 2 weeks postchallenge in the MVA-env and MVA-gag-pol-env groups while the titers remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups. This anamnestic neutralizing antibody response was also detected with T-cell-line-adapted stocks of SIVmac251 and SIV/DeltaB670 but not with SIVmac239, as this latter virus resisted neutralization. Most animals in each group had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge. Titers of neutralizing antibodies were low or undetectable until about 12 weeks of infection in all groups of animals and showed little or no evidence of an anamnestic response when measured with SIVsmE660. The results indicate that recombinant MVA is a promising vector to use to prime for an anamnestic neutralizing antibody response following infection with primate lentiviruses that cause AIDS. However, the Env component of the present vaccine needs improvement in order to target a broad spectrum of viral variants, including those that resemble primary isolates.


2020 ◽  
Author(s):  
Fangzhu Zhao ◽  
Collin Joyce ◽  
Alison Burns ◽  
Bartek Nogal ◽  
Alejandra Ramos ◽  
...  

Author(s):  
Kanika Vanshylla ◽  
Veronica Di Cristanziano ◽  
Franziska Kleipass ◽  
Felix Dewald ◽  
Philipp Schommers ◽  
...  

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