(C) PLOS One
This story was originally published by PLOS One and is unaltered.
 . . . . . . . . . .



Reduced airborne transmission of SARS-CoV-2 BA.1 Omicron virus in Syrian hamsters [1]

['Adrianus C. M. Boon', 'Department Of Medicine', 'Washington University School Of Medicine In St. Louis', 'Missouri', 'United States Of America', 'Department Of Pathology', 'Immunology Washington University School Of Medicine In St. Louis', 'Department Of Microbiology', 'Tamarand L. Darling', 'Peter J. Halfmann']

Date: 2022-12 

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: D.H.B is a co-inventor on provisional vaccine patents (63/121,482; 63/133,969; 63/135,182). The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc., and Nano targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc., for the commercial development of SARS-CoV-2 mAb. M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation, on the Scientific Advisory Boards of Moderna and Immunome, and has licensed mucosal vaccine technology to Bharat Biotech and Ocugen. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. The authors report no other conflict of interest.

Funding: This study was supported by the NIH (R01 AI157155 (MSD), U01 AI151810 (ACMB and MSD), NIAID Centers of Excellence for Influenza Research and Response contract 75N93021C00014 (MSD and YK) and 75N93021C00016 (ACMB, TLD, JF, and RJW). It was also supported, in part, by the National Institutes of Allergy and Infectious Diseases Center for Research on Influenza Pathogenesis (HHSN272201400008C (PJH and YK)), and the Japan Program for Infectious Diseases Research and Infrastructure (JP21wm0125002 (YK)) from the Japan Agency for Medical Research and Development (AMED). JRP and VJM are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). DHB was supported by the Bill & Melinda Gates Foundation (INV-027406). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Since the start of the COVID-19 pandemic, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections worldwide with more than 6.5 million confirmed deaths. SARS-CoV-2 is a respiratory virus that predominantly infects the epithelium of the upper and lower respiratory tract of human and animal hosts. Transmission of respiratory viruses between hosts can occur via direct contact, contact with infected surfaces, or via aerosolized particles [1]. Syrian hamsters are highly susceptible to SARS-CoV-2 infection and one of several animal hosts that have been naturally infected by this virus [2–14]. Transmission of SARS-CoV-2 from pet Syrian hamsters to humans has also been reported [2]. Currently, Syrian hamsters are the only rodent model in which airborne transmission can easily be tested [2,15]. Transmission of SARS-CoV-2 can be established by detection of viral RNA, RNA replication intermediates, viable infectious virus, or seroconversion, with the latter two metrics being the most stringent.

Since January 2021, the National Institutes of Health SARS-CoV-2 Assessment of Variant Evolution (SAVE) initiative has evaluated the transmission potential of SARS-CoV-2 variants in Syrian hamsters [16]. Several SAVE-affiliated laboratories, using variable exposure times (4 to 48 hours), inoculum amounts (103 to 105 infectious units), and experimental designs, observed airborne transmission of SARS-CoV-2 (strain Wuhan-1 or WA1/20202) to nearly 100% of the contact animals. Similar results were obtained with the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617 (Delta) variants of SARS-CoV-2 [15,17,18]. Airborne transmission was associated with high levels of viral RNA and infectious virus in respiratory tissues of the contact animal, and when tested, seroconversion (Fig 1). Certain amino acid mutations (D614G and N501Y) found in the receptor-binding domain of the spike protein of many SARS-CoV-2 variants improved airborne transmission of SARS-CoV-2 in hamsters [19–22]. Late in 2021, the antigenically distinct BA.1 (Omicron) variant emerged. BA.1 viruses were shown to be less pathogenic than prior variants in mice and Syrian hamsters [23,24]. Four SAVE-affiliated laboratories also evaluated BA.1 transmission between hamsters (Fig 1). In direct contact transmission models evaluated in three different laboratories, infectious BA.1 virus was found in 8/10 (80%) of the contact animals. Seroconversion was measured by one laboratory and detected in all three contacts. In contrast, in airborne transmission models, where infected and contact animals are physically separated, infectious BA.1 virus was detected only in 1/13 (7.5%) contact animals. Seroconversion, evaluated in two different laboratories, was detected in the one SARS-CoV-2 RNA replication intermediate positive contact animal. These data suggest that BA.1 airborne transmission is substantially less efficient in hamsters than prior variants. Similar results were obtained for the BA.2.12.2 and BA.5 Omicron variant of SARS-CoV-2. The observations from the SAVE network agree with a recent report [24] evaluating the transmission of BA.1 and BA.2 in hamsters, but contrast with those of Yuan and colleagues [25] who reported, using viral RNA detection methods, efficient airborne transmission of the BA.1 (Omicron) variant of SARS-CoV-2 between hamsters. These results highlight how the metrics used to establish airborne transmission can impact study conclusions, which could affect animal model utilization and even public health messaging.

PPT PowerPoint slide

PNG larger image

TIFF original image Download: Fig 1. Inefficient airborne transmission of BA.1 variant of SARS-CoV-2 in Syrian hamsters. Experimental design and virus titers in the contact animals exposed to different isolates of the Omicron variant of SARS-CoV-2. Kawaoka-laboratory: Five- to six-week-old female Syrian hamsters were inoculated IN with 103 PFUs of the B.1.617.2 (Delta) or BA.1 (Omicron) variant and used as donor animals (grey hamster) in an airborne and direct contact transmission setup. Virus titer in the lungs and NT of the contact animals (brown hamster) was measured by plaque assay 3 dpe. Boon-laboratory: Five- to six-week-old male Syrian hamsters were inoculated IN with 105 PFU of a WA1/2020 virus engineered with a D614G mutation (D614G) or the BA.1 variant and used as donor animals in an airborne transmission setup. In a separate experiment, hamsters were inoculated IN with 103 PFU of the BA.1 variant and used as donor animals in a direct contact transmission setup. Virus titer in the lungs and NWs of the contact animals was measured by plaque assay 3 dpe. Munster-laboratory: Four- to six-week-old male and female Syrian hamsters were inoculated IN with 104 PFU of WA1/2020 or BA.1 variant and used as donor animals in an airborne transmission setup. Additional hamsters were inoculated IN with 104 PFU of the BA.1 variant and used as donor animals in a direct contact transmission setup. Virus titer in OSs taken from the contact animals was measured by RT-qPCR assay 3 dpe, and seroconversion was measured 14 dpe by spike antigen ELISA. Webby-laboratory: Eight- to ten-week-old male Syrian hamsters were inoculated IN with 104 PFU of the WA1/2020 or BA.1 variant and used as donor animals in an airborne transmission setup. Virus titer in the lungs and NT of the contact animals was measured by infectious virus assay 4 dpe, and seroconversion was measured 21 dpe by virus neutralization assay. Each symbol is an individual animal and the bars represent the median value. Dotted line indicates the limit of detection for each respective assay. Green arrow indicates directional airflow. This figure was created with a BioRender template (hamster image). dpe, days postexposure; IN, intranasally; NT, nasal turbinate; NW, nasal wash; OS, oral swab; PFU, plaque-forming unit; RT-qPCR, reverse transcription quantitave PCR. https://doi.org/10.1371/journal.ppat.1010970.g001

Notwithstanding these points, more work is required to understand how well hamsters model SARS-CoV-2 transmission phenotypes in humans, especially for emerging variants. The observation that the BA.1 variant of SARS-CoV-2 does not transmit efficiently via the air in Syrian hamsters appears to contrast with human epidemiological data. The reason for this difference in BA.1 transmission between humans and hamsters is not clear. One possible explanation is the sequence difference in angiotensin-converting enzyme 2 (ACE2) receptor [26], which could impact replication and transmission efficiency of BA.1 in hamsters. The reported attenuation of BA.1 in Syrian hamsters supports this observation [23,24]. However, BA.1 was also attenuated in human ACE2-transgenic hamsters [23], implying that genetic differences in non-spike proteins, which can modulate innate and antiviral immunity, also contribute to the loss of airborne transmission of BA.1 in this model. It has also been reported that the Omicron variant is less dependent on the protease TMPRSS2 for spike protein cleavage and more dependent on cathepsins than the other variants [27–30], implying that the Omicron variant enters cells through a different route. This may have differential effects in humans and hamsters and reduce airborne transmission efficiency of Omicron variants between hamsters. Finally, it is possible that the changes in the spike protein of Omicron affect and reduce stability of the virus in the infected hosts. Differences in pH, salinity, or mucosal barrier between humans and hamsters before or after SARS-CoV-2 infection could contribute to differences in airborne transmission of the BA.1 Omicron variant between humans and hamsters.

To summarize, the combined analysis from multiple groups using different isolates of the BA.1 Omicron variant demonstrate that BA.1 has reduced airborne transmission efficiency in Syrian hamsters compared to prior variants of SARS-CoV-2.

[END]
---
[1] Url: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010970

Published and (C) by PLOS One
Content appears here under this condition or license: Creative Commons - Attribution BY 4.0.

via Magical.Fish Gopher News Feeds:
gopher://magical.fish/1/feeds/news/plosone/