Frontiers in Immunology (Sep 2021)

Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge

  • Elizabeth Gabitzsch,
  • Jeffrey T. Safrit,
  • Mohit Verma,
  • Adrian Rice,
  • Peter Sieling,
  • Lise Zakin,
  • Annie Shin,
  • Brett Morimoto,
  • Helty Adisetiyo,
  • Raymond Wong,
  • Ashish Bezawada,
  • Kyle Dinkins,
  • Joseph Balint,
  • Victor Peykov,
  • Hermes Garban,
  • Philip Liu,
  • Andrew Bacon,
  • Pete Bone,
  • Jeff Drew,
  • Daniel C. Sanford,
  • Patricia Spilman,
  • Lennie Sender,
  • Shahrooz Rabizadeh,
  • Kayvan Niazi,
  • Patrick Soon-Shiong

DOI
https://doi.org/10.3389/fimmu.2021.729837
Journal volume & issue
Vol. 12

Abstract

Read online

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 106 TCID50) SARS-CoV-2 challenge. Notably, viral replication was inhibited within 24 hours of challenge in both lung and nasal passages, becoming undetectable within 7 days post-challenge.

Keywords