Research output: Contribution to journal › Article › peer-review
Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies. / Solodkov, Pavel P.; Najakshin, Alexander M.; Chikaev, Nikolai A. et al.
In: Vaccines, Vol. 12, No. 2, 129, 02.2024.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Serial Llama Immunization with Various SARS-CoV-2 RBD Variants Induces Broad Spectrum Virus-Neutralizing Nanobodies
AU - Solodkov, Pavel P.
AU - Najakshin, Alexander M.
AU - Chikaev, Nikolai A.
AU - Kulemzin, Sergey V.
AU - Mechetina, Ludmila V.
AU - Baranov, Konstantin O.
AU - Guselnikov, Sergey V.
AU - Gorchakov, Andrey A.
AU - Belovezhets, Tatyana N.
AU - Chikaev, Anton N.
AU - Volkova, Olga Y.
AU - Markhaev, Alexander G.
AU - Kononova, Yulia V.
AU - Alekseev, Alexander Y.
AU - Gulyaeva, Marina A.
AU - Shestopalov, Alexander M.
AU - Taranin, Alexander V.
N1 - This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2021-1086, contract No. RF----193021X0015, 15.ИП.21.0015).
PY - 2024/2
Y1 - 2024/2
N2 - The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan’s RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1. We show that initial immunization induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection with the ancestral Wuhan virus. These nanobodies, however, mostly lacked the activity against SARS-CoV-2 omicron-pseudotyped viruses. In contrast, serial immunization with different RBD variants resulted in the generation of nanobodies demonstrating a higher degree of somatic mutagenesis and a broad range of neutralization. Four nanobodies recognizing distinct epitopes were shown to potently neutralize a spectrum of omicron variants, including those of the XBB sublineage. Our data show that nanobodies broadly neutralizing SARS-CoV-2 variants may be readily induced by a serial variant RBD immunization.
AB - The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan’s RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1. We show that initial immunization induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection with the ancestral Wuhan virus. These nanobodies, however, mostly lacked the activity against SARS-CoV-2 omicron-pseudotyped viruses. In contrast, serial immunization with different RBD variants resulted in the generation of nanobodies demonstrating a higher degree of somatic mutagenesis and a broad range of neutralization. Four nanobodies recognizing distinct epitopes were shown to potently neutralize a spectrum of omicron variants, including those of the XBB sublineage. Our data show that nanobodies broadly neutralizing SARS-CoV-2 variants may be readily induced by a serial variant RBD immunization.
KW - COVID-19
KW - SARS-CoV-2
KW - antiviral nanobody
KW - broadly neutralizing antibody
KW - coronavirus variants
KW - single-domain antibody
KW - viral evasion
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85185666872&origin=inward&txGid=f0cc56d191fcddac110ac0774c648e1f
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001172605500001
UR - https://www.mendeley.com/catalogue/4289d137-2325-36d1-910e-9395ca8c26f1/
U2 - 10.3390/vaccines12020129
DO - 10.3390/vaccines12020129
M3 - Article
C2 - 38400113
VL - 12
JO - Vaccines
JF - Vaccines
SN - 2076-393X
IS - 2
M1 - 129
ER -
ID: 61201187