Περίληψη:
The speed of development, versatility and efficacy of mRNA-based
vaccines have been amply demonstrated in the case of SARS-CoV-2. DNA
vaccines represent an important alternative since they induce both
humoral and cellular immune responses in animal models and in human
trials. We tested the immunogenicity and protective efficacy of
DNA-based vaccine regimens expressing different prefusion-stabilized
Wuhan-Hu-1 SARS-CoV-2 Spike antigens upon intramuscular injection
followed by electroporation in rhesus macaques. Different Spike DNA
vaccine regimens induced antibodies that potently neutralized SARS-CoV-2
in vitro and elicited robust T cell responses. The antibodies recognized
and potently neutralized a panel of different Spike variants including
Alpha, Delta, Epsilon, Eta and A.23.1, but to a lesser extent Beta and
Gamma. The DNA-only vaccine regimens were compared to a regimen that
included co-immunization of Spike DNA and protein in the same anatomical
site, the latter of which showed significant higher antibody responses.
All vaccine regimens led to control of SARS-CoV-2
intranasal/intratracheal challenge and absence of virus dissemination to
the lower respiratory tract. Vaccine-induced binding and neutralizing
antibody titers and antibody-dependent cellular phagocytosis inversely
correlated with transient virus levels in the nasal mucosa. Importantly,
the Spike DNA+Protein co-immunization regimen induced the highest
binding and neutralizing antibodies and showed the strongest control
against SARS-CoV-2 challenge in rhesus macaques.
Συγγραφείς:
Rosati, Margherita
Agarwal, Mahesh
Hu, Xintao
Devasundaram,
Santhi
Stellas, Dimitris
Chowdhury, Bhabadeb
Bear, Jenifer
and Burns, Robert
Donohue, Duncan
Pessaint, Laurent and
Andersen, Hanne
Lewis, Mark G.
Terpos, Evangelos
Dimopoulos,
Meletios Athanasios
Wlodawer, Alexander
Mullins, James I. and
Venzon, David J.
Pavlakis, George N.
Felber, Barbara K.
