Max Richard Johnson

All Publications

• Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice. Cell reports Walls, A. C., VanBlargan, L. A., Wu, K., Choi, A., Navarro, M. J., Lee, D., Avena, L., Berrueta, D. M., Pham, M. N., Elbashir, S., Kraft, J. C., Miranda, M. C., Kepl, E., Johnson, M., Blackstone, A., Sprouse, K., Fiala, B., O'Connor, M. A., Brunette, N., Arunachalam, P. S., Shirreff, L., Rogers, K., Carter, L., Fuller, D. H., Villinger, F., Pulendran, B., Diamond, M. S., Edwards, D. K., King, N. P., Veesler, D. 2022: 111299

  Abstract

  The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOCs) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOCs. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses elicited by various vaccine platforms against VOCs, compared with non-human primates or humans, suggesting caution should be exercised when interpreting data obtained with this animal model.

  View details for DOI 10.1016/j.celrep.2022.111299

  View details for PubMedID 35988541

• Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Cell Walls, A. C., Miranda, M. C., Schafer, A., Pham, M. N., Greaney, A., Arunachalam, P. S., Navarro, M., Tortorici, M. A., Rogers, K., O'Connor, M. A., Shirreff, L., Ferrell, D. E., Bowen, J., Brunette, N., Kepl, E., Zepeda, S. K., Starr, T., Hsieh, C., Fiala, B., Wrenn, S., Pettie, D., Sydeman, C., Sprouse, K. R., Johnson, M., Blackstone, A., Ravichandran, R., Ogohara, C., Carter, L., Tilles, S. W., Rappuoli, R., Leist, S. R., Martinez, D. R., Clark, M., Tisch, R., O'Hagan, D. T., Van Der Most, R., Van Voorhis, W. C., Corti, D., McLellan, J. S., Kleanthous, H., Sheahan, T. P., Smith, K. D., Fuller, D. H., Villinger, F., Bloom, J., Pulendran, B., Baric, R. S., King, N. P., Veesler, D. 2021

  Abstract

  Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.

  View details for DOI 10.1016/j.cell.2021.09.015

  View details for PubMedID 34619077

• Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. bioRxiv : the preprint server for biology Walls, A. C., Miranda, M. C., Pham, M. N., Schafer, A., Greaney, A., Arunachalam, P. S., Navarro, M., Tortorici, M. A., Rogers, K., O'Connor, M. A., Shireff, L., Ferrell, D. E., Brunette, N., Kepl, E., Bowen, J., Zepeda, S. K., Starr, T., Hsieh, C., Fiala, B., Wrenn, S., Pettie, D., Sydeman, C., Johnson, M., Blackstone, A., Ravichandran, R., Ogohara, C., Carter, L., Tilles, S. W., Rappuoli, R., O'Hagan, D. T., Van Der Most, R., Van Voorhis, W. C., McLellan, J. S., Kleanthous, H., Sheahan, T. P., Fuller, D. H., Villinger, F., Bloom, J., Pulendran, B., Baric, R., King, N., Veesler, D. 2021

  Abstract

  Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.

  View details for DOI 10.1101/2021.03.15.435528

  View details for PubMedID 33758839