Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

Abstract

COVID-19 vaccines are being developed urgently worldwide, among which single-shot adenovirus vectored vaccines represent a major approach. Here, we constructed two novel adenovirus vectored COVID-19 vaccine candidates on simian adenovirus serotype 23 (Sad23L) and human adenovirus serotype 49 vectors (Ad49L) carrying the full-length gene of SARS-CoV-2 spike protein (S), designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. The immunogenicity elicited by these two vaccine strains was individually evaluated in mice. Specific humoral and cellular immune responses were proportionally observed in a dose-dependent manner, and stronger response was obtained by boosting. Furthermore, five rhesus macaques were intramuscularly injected with a dose of 5×109 PFU Sad23L-nCoV-S vaccine for prime vaccination, followed by boosting with 5×109 PFU of Ad49L-nCoV-S vaccine at 4-week interval. Three macaques were injected with Sad23L-GFP and Ad49L-GFP vectorial viruses as negative controls. Both mice and macaques tolerated well the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost vaccination regimen induced high titers of 103.16 S-binding antibody (S-BAb), 102.75 cell receptor binding domain (RBD)-BAb and 102.38 neutralizing antibody (NAb) to pseudovirus a week after boosting injection, followed by sustained high levels over 10 weeks of observation. Robust IFN-γ secreting T-cell response (712.6 SFCs/106 cells), IL-2 secreting T-cell response (334 SFCs/106 cells) and intracellular IFN-γ expressing CD4+/CD8+ T cell response (0.39%/0.55%) to S peptides were detected in the vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates

“… * Compared to vaccinated groups, 3µg+adjuvant B and 6 µg+adjuvant A; # Compared to the group 6 µg+adjuvant A. T cell response induced by RBD and S1-Fc were not available. Th, T helper response; Y, detected; N, Not detected; ↑, increased as compared to placebo; ↓, decreased compared to vaccinated; NS, not significant; DPI: days post-infection; X, not studied; IFN, interferon; LION, lipid inorganic nanoparticles; TNF-α, tumour necrosis factor-alpha, IL, interleukin Source : Refs 11 12 13 14 17 18 19 20 21 24 25 29 30 32 33 34 35 36 37 …”

“…NVX-CoV2373 33 34 , S-Trimer 35 , RBD 36 , Sad23L-nCoV-S/Ad49L-nCoV-S 37 and S1-Fc 38 were the protein vaccines included in the review.…”

“…Neither gRNA nor sgRNA could be detected in the lung tissues of RBD vaccinated animals in both groups following virus challenge. Virus challenge study was not performed for Sad23L-nCoV-S/Ad49L-nCoV-S vaccine 37 . No data were available for viral clearance from tissues and organs for S1-Fc 38 .…”

“…No data were available for Sad23L-nCoV-S/Ad49L-nCoV-S candidate vaccine. Further, data were not available for histopathological findings of lung tissue in the S1-Fc trial 37 38 .…”

“…Both S-Trimer and Sad23L-nCoV-S/Ad49L-nCoV-S induced NAb response within two weeks of first vaccination, while it took only one week with RBD, three weeks with NVX-CoV2373 and one week with S1-Fc. The titres gradually rose, with peaks at five weeks for S-Trimer and S1-Fc and 4-6 wk for Sad23L-nCoV-S/Ad49L-nCoV-S, and were detectable till five weeks with NVX-CoV2373 and RBD, six weeks with S-Trimer and 10 wk with Sad23L-nCoV-S/Ad49L-nCoV-S 33 35 36 37 38 . NAb titres were higher in animals vaccinated with NVX-CoV2373, S-Trimer and RBD compared to placebo, while control data were not available for Sad23L-nCoV-S/Ad49L-nCoV-S. NVX-CoV2373–vaccinated animals had higher NAb titres than control animals, with increasing titres on booster dose administration 33 35 36 37 38 .…”