Innate and adaptive immune responses to SARS-CoV-2 infection in older golden hamsters

In a recent study published in Cell reportResearchers evaluated the change in symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with age.

In general, viruses that successfully evade the human immune response cause the most illnesses in the elderly. However, new evidence indicates that SARS-CoV-2 selectively targets the elderly population.

About research

In this study, researchers used a golden hamster model to assess differences in innate and immune responses elicited against SARS-CoV-2 between young and elderly animals.

The team obtained two populations of golden hamsters and compared their response to SARS-CoV-2 infection. This was achieved by following the definition of hamster aging. This includes population groups aged 6-9 weeks and over 40 weeks. An intranasal inoculation of the hamster cohort was performed and the presence of SARS-CoV-2 was examined and evaluated 1, 3, 5, and 7 days (dpi) after infection. Viral load.. Lung tissue was collected at each point in time and used to assess viral replication via a plaque assay.

Differences between the two cohorts for viral replication were estimated by performing ribonucleic acid (RNA) sequences in lung samples obtained from uninfected animals representing cohorts of two ages. In addition, host responses in young and elderly animals were characterized by performing RNA sequences on whole lung samples obtained from all time points of infection. The team then characterized humoral and cellular responses by adopting traditional assays in hamster models.

In addition, the team defined cells that are recruited to the lung during SARS-CoV-2 infection by performing flow cytometry. The team also described CD3 + T, CD4 + T, and CD8 +. T cells.. Antibody quality and quantity are determined by enzymatic immunoassay (ELISA) -based quantification of anti-SARS-CoV-2 receptor binding domain (RBD) -specific immunoglobulin G (IgG) and IgG2 antibodies in serological samples. Was also evaluated. ..

result

The results of the study showed that among young hamsters, SARS-CoV-2 levels increased in the early stages of infection, and virus levels increased by 1 and 3 dpi compared to older hamsters. However, the team noted similarities between older hamster cohorts with virus levels of 5 and 7 dpi.

RNA sequences in uninfected samples show at baseline that three pathways, including transforming growth factor beta (TGFβ) and nuclear factor kappa B (NFκB) signaling, were significantly reduced in older animals. it was done. This suggests that the immune response of older animals is altered and may explain the early decline in viral levels in the older cohort. In addition, RNA sequencing of infected samples showed that cytokine induction was also significantly reduced in aged animals.

The team also found that older hamsters had lower levels of chemokine CC motif ligand 2 (CCL2), CCL4, CCL8, CCL28, and the inflammatory cytokine interleukin 1 beta (IL-1β). Overall, this indicates that virus-induced cytokines are increased in older animals on day 3, but do not reach the peak levels exhibited by young animals at 5 and 7 dpi.

The characteristics of humoral and cellular responses showed that the number of immunoconcentrated cells found in lung samples was similar in both age cohorts. In addition, older animals showed a plateau of CD4 + T cells against SARS-CoV-2 infection, with significantly higher baseline concentrations of CD4 + T cells. When it comes to Th1 cells, the team noticed significant upregulation in young animals and downregulation in older animals. Overall, this indicated that T cell proliferation was suppressed among elder hamsters in response to SARS-CoV-2 infection.

The team also showed that characterization of total B cells did not result in significant changes in cell frequency between the young and old animal cohorts. In addition, no detectable differences were found between the two cohorts with respect to B cell class switching.

Quantification of anti-RBD showed no significant age-related differences in antibody production against SARS-CoV-2. However, testing serum samples for efficacy in reducing SARS-CoV-2 infectivity showed that older animals could neutralize the virus by more than 60% compared to younger animals. This suggests that increased levels of suppressor T cells in aged animals may lead to a decrease in germinal center numbers, resulting in suboptimal B cell affinity maturation.

Conclusion

Overall, the study results showed that viral clearance and immune response to SARS-CoV-2 were significantly reduced in the aged hamster population. Researchers believe that future studies need to analyze the effect of age on the adaptive immune response to secondary SARS-CoV-2 infection.