Details

Autor(en) / Beteiligte

• Kwon, Hyung-Joon
• Kosikova, Martina
• Tang, Weichun
• Ortega-Rodriguez, Uriel
• Radvak, Peter
• Xiang, Ruoxuan
• Mercer, Kelly E.
• Muskhelishvili, Levan
• Davis, Kelly
• Ward, Jerrold M.
• Kosik, Ivan
• Holly, Jaroslav
• Kang, Insung
• Yewdell, Jonathan W.
• Plant, Ewan P.
• Chen, Wilbur H.
• Shriver, Mallory C.
• Barnes, Robin S.
• Pasetti, Marcela F.
• Zhou, Bin
• Wentworth, David E.
• Xie, Hang

Titel

Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond

Ist Teil von

• iScience, 2022-12, Vol.25 (12), p.105507-105507, Article 105507

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2022

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2nd dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3rd vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion, and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections. [Display omitted] •COVID-19 vaccine-induced protection against SARS-CoV-2 variants wane after the 2nd dose•Delta and Kappa variants exhibit enhanced virulence in K18-hACE2 mice•Omicron subvariants show greater immune evasion than prior variants Immunology; Immune response; Virology