Pre-existing anti-SARS-CoV-2 immunity reduces viral shedding but increases the competitiveness of SARS-CoV-2 Omicron in hamsters

In a recent study published on the bioRxiv* preprint server, researchers evaluated the impact of pre-existing immunity against severe acute respiratory coronavirus 2 (SARS-CoV-2) acquired from prior infections (PI) or coronavirus disease 2019 (COVID -19) vaccination against the transmission of variants of concern (VOC) of SARS-CoV-2 such as Delta and Omicron.

Study: Infection- or vaccine-mediated immunity reduces SARS-CoV-2 transmission, but increases the competitiveness of Omicron in hamsters. Image Credit: Johannes Menge / Shutterstock


There has been a continuous emergence of SARS-CoV-2 VOCs around the world and the replacement of earlier SARS-CoV-2 VOCs with novel variants has been primarily due to increases in transmissibility of the variants. However, the shedding advantage of Omicron VOC over Delta VOC in humans is not fully understood.

About the study

In the present study, researchers evaluated the impact of pre-existing anti-SARS-CoV-2 immunity on the intrahost and interhost competitiveness of Omicron compared to Delta using Syrian hamsters.

Chain of transmission experiments were performed using naïve, PI, and intramuscular (IM) or intranasal (IN) vaccinated hamsters. The RBD-ACE2 [SARS-CoV-2 spike (S) protein receptor-binding domain-angiotensin-converting enzyme 2] complex was modeled to investigate whether S mutations affected the VOC dynamics of SARS-CoV-2.

SARS-CoV-2 S-facilitated cell entry from Omicron and Delta was compared to the AS lineage by vesicular stomatitis virus (VSV) pseudotype entry assays using ACE2-expressing baby hamster kidney (BHK) cells from hamster or human ACE2.

The team then evaluated the respiratory shedding of SARS-CoV-2 compared to alpha, beta, gamma, delta, or lineage A VOCs. Airborne and contact transmission of Delta and Omicron was evaluated using donor and sentinel hamsters from three generations. . Donor hamsters received IN inoculations of Omicron and Delta in a 1:1 ratio, after which oral swabs, lung tissues, and nasal turbinate samples were examined.

In addition, subgenomic ribonucleic acid (sgRNA) levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and next-generation sequencing (NGS) analysis was performed.

Pre-existing anti-SARS-CoV-2 immune responses were induced by IM or IN AZD1222 vaccines or previous Delta infections. Hamsters (n=6 in each group) were inoculated intranasally with 104 tissue culture infectious doses (TCID50) of Omicron and Delta. The extent of lung damage was assessed based on the lung:body weight ratio of the hamsters.

In addition, anti-S immunoglobulin G (IgG) titers were assessed to quantify immune pressure against Omicron and live virus neutralization assays were performed. the cumulative [area under the curve (AUC)] sgRNA shedding between sentinels and post-IN and post-intratracheal (IT) Omicron inoculation results were compared.


Moderate blockade of airborne transmission (70%) with IM vaccines and >90% blockade of transmission with PI and IN vaccines. Delta outperformed Omicron in directly infected donors and sentinels in all groups, although Omicron was more frequent in hamsters with pre-existing immunity. Immune responses were stronger for Delta, especially in PI hamsters, and decreased SARS-CoV-2 S-mediated cell entry and delayed clearance of Omicron over Delta were observed. For human ACE2, S-mediated entry of Omicron and lineage A was similar and 1.4-fold lower than for Delta VOC and for hamster ACE2, 1.6-fold differences were observed between Omicron and Delta.

Cumulative molt of Alpha-inoculated hamsters was significantly greater than that of Omicron and Gamma-inoculated hamsters. All virgin hamsters were infected by contact transmission, while two sentinel 1 animals (generation 1 sentinels), one sentinel 3 animal, and two sentinel 2 animals were infected by airborne transmission of SARS-CoV-2. No significant differences in sgRNA titers between samples were observed between donor and sentinel hamsters with both routes of transmission combined.

Delta infections showed an increase with each subsequent chain of transmission. Among naive hamsters, SARS-CoV-2 replication was observed in the lungs and nasal turbinates with median values ​​of 8.3 and 6.9 sgRNA copies/gr log10, respectively. In contrast, viral loads were significantly lower for PI, IM, and IN hamsters. In donor hamsters, immunity to PI significantly decreased lung:body weight ratios (1.3, 0.7, 0.8, and 0.8 for naïve, IM, IN, and PI groups, respectively).

Naïve hamsters developed lesions typical of SARS-CoV-2 infection. SARS-CoV-2 nucleoprotein immunoreactivity was most prominent in the periphery of pneumonia foci in the bronchi and alveoli and for cluster differentiation protein 3 (CD3) in the perivascular and peribronchiolar regions. IN vaccines led to four times higher immune responses than IM vaccines and PI hamsters had the highest titers. Neutralizing antibody titers were 10-fold higher for Delta than for Omicron among PI hamsters.

PI and IN vaccines reduced SARS-CoV-2 replication compared to IM vaccines and contact transmission was lower between PI and IN vaccinated hamsters. Naïve hamsters, IM-vaccinated, IN-vaccinated hamsters and PI group showed airborne transmission efficiency of 63%, 29%, 7% and 7%, respectively. Omicron IT inoculation increased SARS-CoV-2 replication and lung pathology, but did not increase transmission and reduced spread in the lower respiratory tract due to reduced affinity of TMPRSS2 (serine transmembrane protease 2) in Omicron due to mutations S.

Overall, the study findings demonstrated that pre-existing immunity and exposure route directly influence the manifestation of COVID-19 and the transmission efficiency of SARS-CoV-2. The data underscore the need to assess the transmission dynamics of SARS-CoV-2 VOCs in populations with pre-existing immunity and address the increasing evolutionary pressures placed on SARS-CoV-2.

*Important news

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.

Magazine Reference:

Julia R. Port, Claude Kwe Yinda, Jade C. Riopelle, Zachary A. Weishampel, Taylor A. Saturday, Victoria A. Avanzato, Jonathan E. Schulz, Myndi G. Holbrook, Kent Barbian, Rose Perry-Gottschalk, Elaine Haddock, Craig Martens, Carl. I. Shaia, Teresa Lambe, Sarah C. Gilbert, Neeltje van Doremalen, Vincent J. Munster. (2022). Infection- or vaccine-mediated immunity reduces SARS-CoV-2 transmission, but increases the competitiveness of Omicron in hamsters. bioRxiv. do: