key: cord-1046674-u50x5uj2 authors: Stauft, Charles B.; Selvaraj, Prabhuanand; Lien, Christopher Z.; Starost, Matthew F.; Wang, Tony T. title: Long‐term immunity in convalescent Syrian hamsters provides protection against new‐variant SARS‐CoV‐2 infection of the lower but not upper respiratory tract date: 2022-02-28 journal: J Med Virol DOI: 10.1002/jmv.27641 sha: ac3e5b168b77ed75af0e03459aca3329e57dcf8b doc_id: 1046674 cord_uid: u50x5uj2 COVID‐19 vaccines provide high levels of protection against severe disease and hospitalization due to severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) infection. Vaccination may be less effective in preventing shedding of infectious viruses from otherwise immune patients. In this study, we describe breakthrough infections and shedding of infectious viruses in convalescent hamsters without significant replication in the lower respiratory tract following reinfection by Alpha and Delta variants despite high levels of circulating antibodies in sera. Using convalescent hamsters with long‐term immunity (up to 1 year) following infection by ancestral SARS‐CoV‐2, we can model aspects of recurring COVID‐19 in the context of preexisting immunity. The ongoing plague of COVID-19 is perhaps the bestdocumented pandemic in human history and the first major threat to global public health to emerge during the age of big data. Almost real-time sequencing of clinical isolates and the availability of this information has led to a wealth of information about viral evolution. Variants of concern continue to emerge and are identified as severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spreads and adapts to its new hosts. Although some beta coronaviruses such as MERS and SARS-CoV-1 were responsible for outbreaks of severe disease, then either faded away or contained, others have become endemic. As SARS-CoV-2 begins to contend with vaccination programs and naturally acquired immunity, infections and deaths continue to occur. Aged Syrian Hamsters recapitulate many aspects of COVID-19 in humans 1,2 including upper respiratory tract (URT), lower respiratory tract (LRT) replication, pathology, and resistance to subsequent infection. 2 postinfection as described previously 9 according to an animal protocol approved by the Food and Drug Administration IACUC. The hamsters were tested for neutralizing antibodies by a 50% plaquereduction neutralization assay 10 just before challenge. A summary of the hamsters used in this study is presented in Table S1 . To compare the ability of Alpha and Delta variants to cause breakthrough infections, convalescent hamsters with long-term immunity The authors declare no conflict of interests. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster does not cause more severe disease, and naturally acquired immunity confers protection. mSphere SARS-CoV-2 infection induces protective immunity and limits transmission in Syrian hamsters Increased close proximity airborne transmission of the SARS-CoV-2 Delta variant Household transmission of COVID-19 cases associated with SARS-CoV-2 delta variant (B.1.617.2): national case-control study The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus Correlation of SARS-CoV-2-breakthrough infections to time-from-vaccine Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study The G614 pandemic SARS-CoV-2 variant is not more pathogenic than the original D614 form in adult Syrian hamsters Extensive genomic recoding by codon-pair deoptimization selective for mammals is a flexible tool to generate attenuated vaccine candidates for dengue virus 2 Long-term immunity in convalescent Syrian hamsters provides protection against new-variant SARS-CoV-2 infection of the lower but not upper respiratory tract