TY - JOUR
T1 - Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
AU - van der Lubbe, Joan E.M.
AU - Rosendahl Huber, Sietske K.
AU - Vijayan, Aneesh
AU - Dekking, Liesbeth
AU - van Huizen, Ella
AU - Vreugdenhil, Jessica
AU - Choi, Ying
AU - Baert, Miranda R.M.
AU - Feddes-de Boer, Karin
AU - Izquierdo Gil, Ana
AU - van Heerden, Marjolein
AU - Dalebout, Tim J.
AU - Myeni, Sebenzile K.
AU - Kikkert, Marjolein
AU - Snijder, Eric J.
AU - de Waal, Leon
AU - Stittelaar, Koert J.
AU - Tolboom, Jeroen T.B.M.
AU - Serroyen, Jan
AU - Muchene, Leacky
AU - van der Fits, Leslie
AU - Rutten, Lucy
AU - Langedijk, Johannes P.M.
AU - Barouch, Dan H.
AU - Schuitemaker, Hanneke
AU - Zahn, Roland C.
AU - Wegmann, Frank
PY - 2021/3/19
Y1 - 2021/3/19
N2 - Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
AB - Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
U2 - 10.1038/s41541-021-00301-y
DO - 10.1038/s41541-021-00301-y
M3 - Article
AN - SCOPUS:85102899071
SN - 2059-0105
VL - 6
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 39
ER -
