Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice
Alexandra C Walls, Laura A VanBlargan, Kai Wu, Angela Choi, Mary Jane Navarro, Diana Lee, Laura Avena, Daniela Montes Berrueta, Minh N Pham, Sayda Elbashir, John C Kraft, Marcos C Miranda, Elizabeth Kepl, Max Johnson, Alyssa Blackstone, Kaitlin Sprouse, Brooke Fiala, Megan A O'Connor, Natalie Brunette, Prabhu S Arunachalam, Lisa Shirreff, Kenneth Rogers, Lauren Carter, Deborah H Fuller, Francois Villinger, Bali Pulendran, Michael S Diamond, Darin K Edwards, Neil P King, David Veesler, Alexandra C Walls, Laura A VanBlargan, Kai Wu, Angela Choi, Mary Jane Navarro, Diana Lee, Laura Avena, Daniela Montes Berrueta, Minh N Pham, Sayda Elbashir, John C Kraft, Marcos C Miranda, Elizabeth Kepl, Max Johnson, Alyssa Blackstone, Kaitlin Sprouse, Brooke Fiala, Megan A O'Connor, Natalie Brunette, Prabhu S Arunachalam, Lisa Shirreff, Kenneth Rogers, Lauren Carter, Deborah H Fuller, Francois Villinger, Bali Pulendran, Michael S Diamond, Darin K Edwards, Neil P King, David Veesler
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.
Trial registration: ClinicalTrials.gov NCT05007951.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; SARS-CoV-2; antibodies; humans; mouse; non-human primates; vaccines.
Conflict of interest statement
Declaration of interests A.C.W., N.P.K., and D.V. are named as inventors on patent applications filed by the University of Washington based on the RBD-NP presented in this paper. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc., and the King lab has received an unrelated sponsored research agreement from Pfizer. M.S.D. is a consultant for Inbios, Vir Biotechnology, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. K.W., A.C., and D.K.E are employees of Moderna and hold stock/stock options in the company. D.H.F. has equity interest in HDT Bio.
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Figures
References
- Amanat F., Strohmeier S., Meade P.S., Dambrauskas N., Mühlemann B., Smith D.J., Vigdorovich V., Sather D.N., Coughlan L., Krammer F. Vaccination with SARS-CoV-2 variants of concern protects mice from challenge with wild-type virus. PLoS Biol. 2021;19:e3001384.
- Arunachalam P.S., Feng Y., Ashraf U., Hu M., Walls A.C., Edara V.V., Zarnitsyna V.I., Aye P.P., Golden N., Miranda M.C., et al. Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine. Sci Transl Med. 2022;14:eabq4130.
- Arunachalam P.S., Walls A.C., Golden N., Atyeo C., Fischinger S., Li C., Aye P., Navarro M.J., Lai L., Edara V.V., et al. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity. Nature. 2021;594:253–258.
- Bale J.B., Gonen S., Liu Y., Sheffler W., Ellis D., Thomas C., Cascio D., Yeates T.O., Gonen T., King N.P., et al. Accurate design of megadalton-scale two-component icosahedral protein complexes. Science. 2016;353:389–394.
- Cameroni E., Bowen J.E., Rosen L.E., Saliba C., Zepeda S.K., Culap K., Pinto D., VanBlargan L.A., De Marco A., di Iulio J., et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2021;602:664–670.
- Case J.B., Rothlauf P.W., Chen R.E., Liu Z., Zhao H., Kim A.S., Bloyet L.-M., Zeng Q., Tahan S., Droit L., et al. Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2. Cell Host Microbe. 2020;28:475–485.e5.
- Case J.B., Bailey A.L., Kim A.S., Chen R.E., Diamond M.S. Growth, detection, quantification, and inactivation of SARS-CoV-2. Virology. 2020;548:39–48.
- Chen R.E., Zhang X., Case J.B., Winkler E.S., Liu Y., VanBlargan L.A., Liu J., Errico J.M., Xie X., Suryadevara N., et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 2021;27:717–726.
- Collier D.A., The CITIID-NIHR BioResource COVID-19 Collaboration. De Marco A., Ferreira I.A.T., Meng B., Datir R.P., Walls A.C., Kemp S.A., Bassi J., Pinto D., et al. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies. Nature. 2021;593:136–141.
- Corbett K.S., Nason M.C., Flach B., Gagne M., O’Connell S., Johnston T.S., Shah S.N., Edara V.V., Floyd K., Lai L., et al. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science. 2021;373:eabj0299.
- Corti D., Purcell L.A., Snell G., Veesler D. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell. 2021;184:4593–4595.
- Crawford K.H.D., Eguia R., Dingens A.S., Loes A.N., Malone K.D., Wolf C.R., Chu H.Y., Tortorici M.A., Veesler D., Murphy M., et al. Protocol and reagents for pseudotyping lentiviral particles with SARS-CoV-2 spike protein for neutralization assays. Viruses. 2020;12:513.
- Fiege J.K., Block K.E., Pierson M.J., Nanda H., Shepherd F.K., Mickelson C.K., Stolley J.M., Matchett W.E., Wijeyesinghe S., Meyerholz D.K., et al. Mice with diverse microbial exposure histories as a model for preclinical vaccine testing. Cell Host Microbe. 2021;29:1815–1827.e6.
- Gibson D.G., Young L., Chuang R.Y., Venter J.C., Hutchison C.A., Smith H.O. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods. 2009;6:343–345.
- Gilbert P.B., Montefiori D.C., McDermott A.B., Fong Y., Benkeser D., Deng W., Zhou H., Houchens C.R., Martins K., Jayashankar L., et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science. 2021;375:43–50.
- Gralinski L.E., Ferris M.T., Aylor D.L., Whitmore A.C., Green R., Frieman M.B., Deming D., Menachery V.D., Miller D.R., Buus R.J., et al. Genome wide identification of SARS-CoV susceptibility loci using the collaborative cross. PLoS Genet. 2015;11:e1005504.
- Greaney A.J., Loes A.N., Crawford K.H.D., Starr T.N., Malone K.D., Chu H.Y., Bloom J.D. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe. 2021;29:463–476.e6.
- Hassan A.O., Feldmann F., Zhao H., Curiel D.T., Okumura A., Tang-Huau T.-L., Case J.B., Meade-White K., Callison J., Chen R.E., et al. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Rep. Med. 2021;2:100230.
- Hsieh C.-L., Goldsmith J.A., Schaub J.M., DiVenere A.M., Kuo H.-C., Javanmardi K., Le K.C., Wrapp D., Lee A.G., Liu Y., et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science. 2020;369:1501–1505.
- Kaname Y., Tani H., Kataoka C., Shiokawa M., Taguwa S., Abe T., Moriishi K., Kinoshita T., Matsuura Y. Acquisition of complement resistance through incorporation of CD55/decay-accelerating factor into viral particles bearing baculovirus GP64. J. Virol. 2010;84:3210–3219.
- Lee E.-C., Liang Q., Ali H., Bayliss L., Beasley A., Bloomfield-Gerdes T., Bonoli L., Brown R., Campbell J., Carpenter A., et al. Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery. Nat. Biotechnol. 2014;32:356–363.
- Lempp F.A., Soriaga L.B., Montiel-Ruiz M., Benigni F., Noack J., Park Y.-J., Bianchi S., Walls A.C., Bowen J.E., Zhou J., et al. Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies. Nature. 2021;598:342–347.
- Martinez D.R., Schäfer A., Leist S.R., De la Cruz G., West A., Atochina-Vasserman E.N., Lindesmith L.C., Pardi N., Parks R., Barr M., et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science. 2021;373:991–998.
- McCallum M., Walls A.C., Sprouse K.R., Bowen J.E., Rosen L.E., Dang H.V., deMarco A., Franko N., Tilles S.W., Logue J., et al. Molecular basis of immune evasion by the delta and kappa SARS-CoV-2 variants. Science. 2021;374:1621–1626.
- Mlcochova P., Kemp S., Dhar M.S., Papa G., Meng B., Mishra S., Whittaker C., Mellan T., Ferreira I., Datir R. SARS-CoV-2 B. 1.617. 2 Delta variant emergence, replication and sensitivity to neutralising antibodies. bioRxiv. 2021 doi: 10.1101/2021.05.08.443253. Preprint at.
- Murphy A.J., Macdonald L.E., Stevens S., Karow M., Dore A.T., Pobursky K., Huang T.T., Poueymirou W.T., Esau L., Meola M., et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc. Natl. Acad. Sci. USA. 2014;111:5153–5158.
- Nie J., Xie J., Liu S., Wu J., Liu C., Li J., Liu Y., Wang M., Zhao H., Zhang Y., et al. Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants. Cell Discov. 2021;7:53.
- Pallesen J., Wang N., Corbett K.S., Wrapp D., Kirchdoerfer R.N., Turner H.L., Cottrell C.A., Becker M.M., Wang L., Shi W., et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc. Natl. Acad. Sci. USA. 2017;114:E7348–E7357.
- Sauer M.M., Tortorici M.A., Park Y.-J., Walls A.C., Homad L., Acton O.J., Bowen J.E., Wang C., Xiong X., de van der Schueren W., et al. Structural basis for broad coronavirus neutralization. Nat. Struct. Mol. Biol. 2021;28:478–486.
- Song J.Y., Choi W.S., Heo J.Y., Lee J.S., Jung D.S., Kim S.W., Park K.H., Eom J.S., Jeong S.J., Lee J., et al. Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial. EClinicalMedicine. 2022;51:101569.
- Tegally H., Wilkinson E., Giovanetti M., Iranzadeh A., Fonseca V., Giandhari J., Doolabh D., Pillay S., San E.J., Msomi N., et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv. 2020 doi: 10.1101/2020.12.21.20248640. Preprint at.
- VanBlargan L.A., Adams L.J., Liu Z., Chen R.E., Gilchuk P., Raju S., Smith B.K., Zhao H., Case J.B., Winkler E.S., et al. A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope. Immunity. 2021;54:2399–2416.e6.
- Walls A.C., Fiala B., Schäfer A., Wrenn S., Pham M.N., Murphy M., Tse L.V., Shehata L., O’Connor M.A., Chen C., et al. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2. Cell. 2020;183:1367–1382.e17.
- Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;183:281–292.e6.
- Walls A.C., Miranda M.C., Schäfer A., Pham M.N., Greaney A., Arunachalam P.S., Navarro M.-J., Tortorici M.A., Rogers K., O’Connor M.A., et al. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Cell. 2021;184:5432–5447.e16.
- Walls A.C., Sprouse K.R., Bowen J.E., Joshi A., Franko N., Navarro M.J., Stewart C., Cameroni E., McCallum M., Goecker E.A., et al. SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses. Cell. 2022;185:872–880.e3.
- Wang C., Li W., Drabek D., Okba N.M.A., van Haperen R., Osterhaus A.D.M.E., van Kuppeveld F.J.M., Haagmans B.L., Grosveld F., Bosch B.-J. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun. 2020;11:2251.
- Whitt M.A. Generation of VSV pseudotypes using recombinant ΔG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines. J. Virol. Methods. 2010;169:365–374.
- Wu K., Choi A., Koch M., Elbashir S., Ma L., Lee D., Woods A., Henry C., Palandjian C., Hill A., et al. Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice. Vaccine. 2021;39:7394–7400.
- Ying B., Whitener B., VanBlargan L.A., Hassan A.O., Shrihari S., Liang C.-Y., Karl C.E., Mackin S., Chen R.E., Kafai N.M., et al. Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains. Sci. Transl. Med. 2022;14:eabm3302.
Source: PubMed