Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

Abstract

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 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 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.

Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients

“…Sera were analyzed on the day of vaccination (day 1), 1 and 3 weeks later (day 8, day 22), and 2 and 4 weeks after the 2 nd vaccination (day 36 and day 50). We found strong correlations (Figures S1A-S1C) between anti-Spike-RBD (Figure 1A) and Spike (Figure 1B) antibodies, which is in agreement with our previous reports using sera from SARS-CoV-2 convalescent patients and Spike-DNA-vaccinated macaques (Rosati et al, 2021;Terpos et al, 2020Terpos et al, , 2021a and supports the notion that RBD is the major antibody target.…”

“…Overall NAb levels followed those of the binding antibodies. The pseudotype NAb levels correlated significantly with the anti-Spike-RBD (Figure S2A) and anti-Spike antibodies (Figure S2B), as expected from our studies of convalescent patients and of vaccinated macaques (Rosati et al, 2021;Terpos et al, 2020Terpos et al, , 2021a, supporting that antibody measurements (Spike and Spike-RBD) can serve as surrogates for NAb measurements.…”

Immunogenicity of the DNA/Protein Combined Vaccine against COVID-19

“…3). Similar results were obtained by simultaneous immunization of rhesus macaques with DNA vaccine and SARS-CoV-2 spike protein [11].…”

T cells in SARS-CoV-2 infection and vaccination

“… 133 A spike DNA plus protein vaccine was electroporated into rhesus macaques and induced a robust T-cell response. 134 A spike-ferritin nanoparticle vaccine with Alhydrogel and Army Liposome Formulation adjuvants given to mice produced a polyfunctional memory CD4 + T cell as well as a long-lived memory CD8 + T-cell response. 135 Intradermal delivery of N with a dissolvable microneedle skin patch induced a significant T-cell response in mice.…”