Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model
immunology/immunity therapeutics vaccines virology
Authors: Ami Patel†1, Jewell Walters†2, Emma L. Reuschel†1, Katherine Schultheis†2, Elizabeth Parzych†1, Ebony N. Gary†1, Igor Maricic2, Mansi Purwar1, Zeena Eblimit2, Susanne N. Walker1, Diana Guimet2, Pratik Bhojnagarwala1, Arthur Doan2, Ziyang Xu1, Dustin Elwood2, Sophia M. Reeder1, Laurent Pessaint3, Kevin Y. Kim1, Anthony Cook3, Neethu Chokkalingam1, Brad Finneyfrock3, Edgar Tello-Ruiz1, Alan Dodson3, Jihae Choi1, Alison Generotti2, John Harrison3, Nicholas J. Tursi1, Viviane M. Andrade2, Yaya Dia1, Faraz I. Zaidi1, Hanne Andersen3, Mark G. Lewis3, Kar Muthumani1, J Joseph Kim2, Daniel W. Kulp1, Laurent M. Humeau2, Stephanie Ramos2, Trevor R.F. Smith2, David B. Weiner1* and Kate E. Broderick2*
Journal/ Pre-Print: bioRxiv
Tags; Immunology/Immunity, Therapeutics, Vaccines, Virology
1. Two 1 mg injections to non-human primates of a potential COVID-19 DNA vaccine (INO-4800 ) encoding the SARS-CoV-2 IgE-spike, leads to development of IgG antibodies (blood samples and bronchoalveolar lavage (BAL)), and reactive T-cell immune responses.
2. Although, viral sgmRNA was detected in nasal swabs of both, in control and INO 4800 vaccinated animals, viral sgnRNA was reduced in the BAL from INO-4800 vaccinated group by day 7 post-challenge
3. Blood samples were collected every two weeks until week 15 and post-challenge every day until day 4th followed by a sample collection on day 7th. By day 7 post-challenge all vaccinated animals has increased antibody titres against S1+S2 extracellular domain (ECD), S1, RBD and S2 proteins, and showed neutralisation activity against a pseudovirus at d14 post-challenge. SARS-CoV-2 antigen reactive T cells responses peaked at week 6
Rhesus macaques (n=5) received two 1mg intradermal injections of SARS-CoV-2 DNA vaccine at week 0 and 4 followed by intranasal and intratracheal challenge after 13 weeks. All vaccinated animals had increased antibody titres against ECD, S1, RBD and S2 proteins compared to 1/5 in the control group (n=5) by day 7 post-challenge, demonstrating a boosting effect of the challenge in the vaccinated animals.
SARS-CoV-2 reactive IgG against ECD, S1, S2 and RBD were detected in bronchoalveolar lavage at week 8. Additionally, SARS-CoV-2 antigen reactive T-cell responses peaked at week 6. Although, viral sgnRNA was detected in nasal swabs of both, in control and INO 4800 vaccinated animals, viral sgnRNA was reduced in the BAL from INO-4800 vaccinated group by day 7 post-challenge.
Impact for SARS-CoV2/COVID19 research efforts
Develop a vaccine for SARS-CoV2/COVID19
Pre-clinical study (non-human primates (total n=10))
Strengths and limitations of the paper
Novelty: Animal model evaluating immunological responses of SARS-CoV-2 IgE-spike DNA vaccine; Late timepoint challenge (4 months).
Standing in the field: see. Translatability
Appropriate statistics: Small sample size
Viral model used: Non-human primates received intranasal and intratracheal challenge SARS-Related Coronavirus 2 after 13 weeks
Translatability: Real efficacy and protection not known since clinical scores and lung histologic findings are missing
Small sample size (5 participants each group)
Real efficacy and protection not known since clinical scores and lung histologic findings are missing.
Lack of T-cell phenotypes