Immunity
. 2021 Feb 4;S1074-7613(21)00042-X.
doi: 10.1016/j.immuni.2021.02.001. Online ahead of print.
A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs
Nanda Kishore Routhu 1 , Narayanaiah Cheedarla 1 , Sailaja Gangadhara 1 , Venkata Satish Bollimpelli 1 , Arun K Boddapati 2 , Ayalnesh Shiferaw 1 , Sheikh Abdul Rahman 1 , Anusmita Sahoo 1 , Venkata Viswanadh Edara 3 , Lilin Lai 3 , Katharine Floyd 3 , Shelly Wang 4 , Stephanie Fischinger 5 , Caroline Atyeo 5 , Sally A Shin 5 , Sanjeev Gumber 6 , Shannon Kirejczyk 6 , Joyce Cohen 7 , Sherrie M Jean 7 , Jennifer S Wood 7 , Fawn Connor-Stroud 7 , Rachelle L Stammen 7 , Amit A Upadhyay 4 , Kathryn Pellegrini 4 , David Montefiori 8 , Pei-Yong Shi 9 , Vineet D Menachery 10 , Galit Alter 5 , Thomas H Vanderford 4 , Steven E Bosinger 2 , Mehul S Suthar 3 , Rama Rao Amara 11
Affiliations
- PMID: 33631118
- DOI: 10.1016/j.immuni.2021.02.001
Abstract
A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8+ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8+ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
Keywords: CD8 T cells; COVID-19; Modified Vaccinia Ankara; Neutralizing antibody; Protection; Rhesus macaques; SARS-CoV-2; Spike; Vaccine.