• MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

      Coleman, C.M.; Venkataraman, T.; Frieman, M.B. (Elsevier Ltd, 2017)
      The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.
    • One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

      Gu, Maggie; Torres, Jonathan L; Li, Yijia; Ry, Alex Van; Greenhouse, Jack; Wallace, Shannon; Chiang, Chi-I; Pessaint, Laurent; Jackson, Abigail M; Porto, Maciel; et al. (Taylor and Francis Inc., 2021-10-15)
      A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ∼10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.