Immune memory from SARS-CoV-2 infection in hamsters provides variant-independent protection but still allows virus transmission

Abstract

SARS-CoV-2 has caused significant morbidity and mortality across the globe. As the virus spreads, new variants are arising that show enhanced capacity to bypass pre-existing immunity. To understand the memory response to SARS-CoV-2, here we monitored SARS-CoV-2-specific T and B cells in a longitudinal study of infected and recovered golden hamsters. We demonstrated that engagement of the innate immune system following SARS-CoV-2 infection was delayed but was followed by a pronounced adaptive response. Moreover, T cell adoptive transfer conferred a reduction in virus levels and rapid induction of SARS-CoV-2specific B cells demonstrating both lymphocyte populations contributed to the overall response. Reinfection of recovered animals with a SARS-CoV-2 variant of concern showed that SARS-CoV-2-specific T and B cells could effectively control the infection which associated with the rapid induction of neutralizing antibodies but failed to block transmission to both naïve and seroconverted animals. These data suggest that the adaptive immune response to SARS-CoV-2 is sufficient to provide protection to the host, independent of the emergence of novel variants.

SARS-CoV-2 infection results in lasting and systemic perturbations post recovery

“…To explore whether this proinflammatory signal was present in additional anatomical regions linked to the olfactory bulb, olfactory epithelium was harvested from hamsters infected with SARS-CoV-2, IAV, or PBS (mock) at 30dpi as this tissue has been demonstrated to harbor infectious virus (Hoagland et al ., 2021; Horiuchi et al, 2021). Ontological analyses of mRNA-Seq data demonstrated that, similar to the olfactory bulbs, the olfactory epithelium of SARS-CoV-2-infected hamsters uniquely showed upregulated signatures for IFN-I and IFN-II (Figure 5J and S6D).…”

“…At 31dpi, the olfactory bulb of IAV-infected hamsters returned to a baseline transcriptional state while the same region of SARS-CoV-2-infected hamsters appeared to be in the midst of an ongoing infection characterized by microglial activation and a robust IFN-I and chemokine response. This was especially surprising given that we were unable to detect presence of viral RNA in either the olfactory bulb or lungs at this time point and, demonstrated previously, we know that hamsters generate a strong anti-S antibody response as early as seven days post infection (Hoagland et al ., 2021; Horiuchi et al ., 2021). Immunohistochemistry of MX1 corroborated our transcriptional findings and showed localization of this persistent IFN-I response to the glomerular regions of the olfactory bulbs.…”

“…Given the olfactory bulbs were positive for SARS-CoV-2 early in infection, these data may suggest either an undetectable level of replication is persisting in an adjacent region or that left-over debris is responsible for the continued inflammatory profile. Our inability to isolate infectious virus from hamsters from any tissue after seven days post infection would provide support for the latter hypothesis, although others have reported the ability to detect replication-competent virus from comparable tissues (de Melo et al ., 2021; Hoagland et al ., 2021; Horiuchi et al ., 2021).…”

Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues

“…For example, T cells likely play a significant role when SARS-CoV-2 infection does not resolve quickly, such as during moderate and severe COVID-19. T cells have been implicated in control of SARS-CoV-2 in other susceptible animal models, like the human ACE2 expressing mouse lines and Syrian hamsters [78][79][80] . Furthermore, nucleocapsid specific CD8 T cells are correlated with less severe disease in patients 20 .…”

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

“…We did not investigate vaccine-induced T-cell responses, which may play critical roles in protection against severe COVID-19, particularly in the context of variants [43][44][45][46][47][48][49][50] . Furthermore, our assays tested only the ancestral SARS-CoV-2 strain (Wuhan or USA-WA1/2020); assessments of SARS-CoV-2 variants including Omicron are in progress.…”