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TitleProtein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.
Journal, issue, pagesCell Rep, Vol. 43, Issue 12, Page 115036, Year 2024
Publish dateDec 24, 2024
AuthorsCara W Chao / Kaitlin R Sprouse / Marcos C Miranda / Nicholas J Catanzaro / Miranda L Hubbard / Amin Addetia / Cameron Stewart / Jack T Brown / Annie Dosey / Adian Valdez / Rashmi Ravichandran / Grace G Hendricks / Maggie Ahlrichs / Craig Dobbins / Alexis Hand / Jackson McGowan / Boston Simmons / Catherine Treichel / Isabelle Willoughby / Alexandra C Walls / Andrew T McGuire / Elizabeth M Leaf / Ralph S Baric / Alexandra Schäfer / David Veesler / Neil P King /
PubMed AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few ...Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nanoparticles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
External linksCell Rep / PubMed:39644492 / PubMed Central
MethodsEM (single particle)
Resolution15.0 Å
Structure data

EMDB-47577: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV NTD-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47580: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47583: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47584: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47585: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47586: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P-T33_dn10 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47587: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV S-2P-T33_dn10 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47588: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV RBD-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47589: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV RBD-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

EMDB-47592: Negative stain EM map of polyclonal serum from mouse immunized with MERS-CoV RBD-I53-50 in complex with MERS S-2P
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Mus musculus (house mouse)

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