Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Abstract

Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following reinfection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity.Research in contextEvidence before this studySecondary infections with Delta variant are being widely reported and there are reports of increased disease severity. Delta sub lineages with K417N substitution has caused concern worldwide due to the presence of the same substitution in Beta variant, a Variant of Concern known for its immune evasion. The information on the biological characteristics of this sub lineage is also scanty.Added value of this studyThe present study showed that the secondary infection with Delta variant does not show any evidence of increased disease severity in hamster model. Delta AY. 1 variant produces mild disease in Syrian hamsters in contrast to severe disease caused by Delta variant. Delta, B.1 and AY.1 variant infected hamster sera showed comparable cross neutralizing response against each other. In contrast to the lower neutralizing response shown by B.1 and Delta variant infected animals against B.1.351 variant, Delta AY.1 showed comparable response as that with other variants.Implications of the available evidenceSARS-CoV-2 infections do not produce sterilizing immunity but protect from developing severe disease in case of Delta variant re-infection indicating the importance of the transmission prevention efforts even after achieving herd immunity. Delta AY. 1 infection in hamsters did not show any evidence of speculated immune evasion.

Booster vaccines protect hamsters with waning immunity from Delta VOC infection, disease, and transmission

“…2a). These data confirm waning immunity to mRNA vaccination against SARS-CoV-2 in the golden Syrian hamster, as was shown recently after natural infection 28,29 . The similarity to which serum NAb titers were generated and then waned relative to humans provides support for the hamster as a high-fidelity model for studying booster vaccination 30,31 .…”

“…Collectively, these data show that hamsters with waning immunity to bnt162b2 are highly susceptible to URT infection by Delta VOC but clear it faster than unvaccinated animals and are modestly- to highly susceptible to infection and associated inflammation in the lung, respectively. A qualitatively similar response was recently reported in hamsters with waning immunity to natural infection 28,29 .…”

Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters

“…Mucosal COVID-19 vaccines have been experimentally shown to reduce upper respiratory shedding, but not transmission, when assessed in a single contact transmission chain setting [ 30 – 32 ]. In addition, hamster studies have shown that previous infection protects against disease, but not upper respiratory tract replication, after homologous and heterologous reinfection [ 27 , 34 – 36 ]. Similar dynamics were observed in our experimental setup.…”