Impact of Reinfection with SARS-CoV-2 Omicron Variants in Previously Infected Hamsters

Shiwa-Sudo, Nozomi; Sakai, Yusuke; Iwata‐Yoshikawa, Naoko; Watanabe, Shinji; Yamada, Souichi; Kuroda, Yudai; Yamamoto, Tsukasa; Saijo, Masayuki; Fujisaki, Seiichiro; Miyazaki, Kaya; Miura, Hideka; Nagata, Shiho; Fukushi, Shuetsu; Maeda, Ken; Hasegawa, Hideki; Suzuki, Tadaki; Nagata, Noriyo

doi:10.1128/jvi.01366-22

Cited by 5 publications

(7 citation statements)

References 61 publications

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“…The Syrian golden hamster has become the preclinical animal model of choice to assess vaccine effectiveness against SARS-CoV-2 variants, as well as the likelihood of reinfections ( 16 , 21 – 28 ). Such information is critical for rational decisions around vaccine strain updates or other public health responses to the continuing emergence of new variants.…”

Section: Discussionmentioning

confidence: 99%

Omicron breakthrough infections in vaccinated or previously infected hamsters

Zhou,

Sukhova,

Peacock

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The ongoing SARS-CoV-2 epidemic was marked by the repeated emergence and replacement of “variants” with genetic and phenotypic distance from the ancestral strains, the most recent examples being viruses of the Omicron lineage. Here, we describe a hamster direct contact exposure challenge model to assess protection against reinfection conferred by either vaccination or prior infection. We found that two doses of self-amplifying RNA vaccine based on the ancestral Spike ameliorated weight loss following Delta infection and decreased viral loads but had minimal effect on Omicron BA.1 infection. Prior vaccination followed by Delta or BA.1 breakthrough infections led to a high degree of cross-reactivity to all tested variants, suggesting that repeated exposure to antigenically distinct Spikes, via infection and/or vaccination drives a cross-reactive immune response. Prior infection with ancestral or Alpha variant was partially protective against BA.1 infection, whereas all animals previously infected with Delta and exposed to BA.1 became reinfected, although they shed less virus than BA.1-infected naive hamsters. Hamsters reinfected with BA.1 after prior Delta infection emitted infectious virus into the air, indicating that they could be responsible for onwards airborne transmission. We further tested whether prior infection with BA.1 protected from reinfection with Delta or later Omicron sublineages BA.2, BA.4, or BA.5. BA.1 was protective against BA.2 but not against Delta, BA.4, or BA.5 reinfection. These findings suggest that cohorts whose only immune experience of COVID-19 is Omicron BA.1 infection may be vulnerable to future circulation of reemerged Delta-like derivatives, as well as emerging Omicron sublineages.

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Section: Discussionmentioning

confidence: 99%

Omicron breakthrough infections in vaccinated or previously infected hamsters

Zhou,

Sukhova,

Peacock

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…With human clinical data examining multiple exposures to coronaviruses 12,63,64,71,72 , including SARS-CoV-2 [73][74][75][76][77][78] , being inconsistent due to host factors and co-morbidities, it is essential to have the ability to study infection-reinfection in appropriate animal models for experimental variable isolation. Ferrets 79,80 , hamsters [81][82][83][84][85][86][87][88] , and non-human primates 89,90 , have all been used to study secondary challenge with SARS-CoV-2. While a primary exposure to the SARS-CoV-2 ancestral strain in rhesus macaques can lead to weight loss, viral load in respiratory and gastrointestinal tracts as well as lung damage, a reinfection with the same virus on day 28 post primary inoculation led to protection 89 .…”

Section: Discussionmentioning

confidence: 99%

“…In homologous reinfection experiments with ferrets, secondary challenge with SARS-CoV-2 Wuhan at day 28 or 56 post initial inoculation still maintained protection with no clinical signs reported or viral load detected 79,80 . Multiple studies have assessed infection-reinfection with the ancestral SARS-CoV-2 as well as variants revealing that while even heterologous reinfection with different variants decreases clinical signs and the presence of live virus, previous exposure to a SARS-CoV-2 virus does not lead to complete protection [81][82][83][84][85][86][87][88] . Hansen et al, assessed homologous reinfection with SARS-CoV-2 Wuhan, with the secondary challenge occurring at day 14, 49 and 152 days post primary and found that day 49 reinfection, the time point closest to our experimental design with a day 56 reinfection, was the most protective 85 .…”

Section: Discussionmentioning

confidence: 99%

“…Hansen et al, assessed homologous reinfection with SARS-CoV-2 Wuhan, with the secondary challenge occurring at day 14, 49 and 152 days post primary and found that day 49 reinfection, the time point closest to our experimental design with a day 56 reinfection, was the most protective 85 . Shiwa-Sudo and colleagues observed increases in T cell activity correlated with earlier viral clearance 87 . These findings were consistent not only with our variant reinfections where we observed increases in T cell related gene expression, but also in OC43-Wuhan animals where virus levels were lower in the nasal turbinates and lung compared to mock-Wuhan animals, although noted not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

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Signatures of Original Antigenic Sin or protection following coronavirus imprinting in Syrian hamsters challenged with SARS-CoV-2 or variants

Francis¹,

Jansen²,

Yourkowski³

et al. 2023

Preprint

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Coronaviruses are a significant threat to public health, animal welfare, and economic stability. SARS-CoV-2 and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Immunological imprinting is a term meant to represent the strong influence of the first viral infection on the outcome of subsequent related viral infections or vaccination, with “Original Antigenic Sin” having historically been applied to the potential negative effects of such imprinting. Little is known, however, about the imprinting potential between seasonal and severe coronaviruses of zoonotic origin and the regulation of cross-reactive responses, positive or negative, upon secondary or subsequent exposures. Here we adopted a step-wise experimental approach to examine the imprinting response and subsequent immune recall toward antigenically distinct coronaviruses at various distances using the Syrian hamster model. This approach enabled the experimental evaluation of cross-reactivity and cross-protection among coronaviruses which has not been previously done. Hamsters were imprinted with seasonal coronaviruses including alphacoronaviruses (HCoV-NL63, HCoV-229E) and betacoronaviruses (HCoV-OC43), or the original SARS-CoV-2 Wuhan virus (also a betacoronavirus). Seasonal CoV imprinting was followed by challenge with the original SARS-CoV-2 Wuhan virus representing distant imprinting-challenge combinations. Wuhan imprinting was followed by homologous Wuhan challenge or heterologous Beta or Omicron variants of concern to assess responses along a continuum of SARS-CoV-2 inter-relatedness. Weight loss and temperature as well as viral load, antibody induction, and host gene profiling for interferon responses, inflammation, and germinal center reactions were analyzed. Although imprinting with seasonal coronaviruses offered little protection against a SARS-CoV-2 Wuhan challenge in terms of viral replication and weight loss, NL63 imprinted animals mounted antigenic sin-like antibody responses while T cell gene signatures were noted in OC43 imprinted animals. The more similar imprinting-challenge regimens led to minimal or no viral replication. Subtle differences in the host responses were noted between Omicron and Beta challenges, suggesting Omicron to be more antigenically distant from Wuhan than the Beta variant. Host gene expression profiling analysis indicated interferon responses and germinal center reactions to be induced during more similar imprinting-challenge combinations while inflammation and antiviral response suppression were signatures in antigenically distant viral challenges. This work is the first characterization and analysis of seasonal coronavirus infection in animals and the subsequent effects on secondary SARS-CoV-2 infection. These results are important for calculating the antigenic distance between coronaviruses and for determining positive or negative cross-reactive signatures. As we begin to construct a matrix of protection, these data may inform the design of pan-coronavirus vaccines and the components needed in a multivalent platform to protect against antigenically distinct groups of coronaviruses while mitigating the risk of negative interference.

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“…The possession of both α2,6- and α2,3-linked sialic acid receptors means that hamsters are a suitable model for comparative studies between viruses with different sialic acid specificities, for example, human and avian viruses. Hamsters have been used extensively over the past three years in SARS-CoV-2 studies to assess the pathogenesis of emerging variants [ 32 , 33 , 34 ], the effect of countermeasures [ 35 , 36 , 37 ] and the impact of co-infection with influenza [ 38 ] or adenovirus [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters

Paterson¹,

Ryan²,

Morley³

et al. 2023

Pathogens

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Animal models of influenza are important in preclinical research for the study of influenza infection and the assessment of vaccines, drugs and therapeutics. Here, we show that Golden Syrian hamsters (Mesocricetus auratus) inoculated via the intranasal route with high dose of influenza H1N1 display comparable disease kinetics and immune responses to the ‘gold standard’ ferret (Mustela furo) model. We demonstrate that both the hamster and ferret models have measurable disease endpoints of weight loss, temperature change, viral shedding from the upper respiratory tract and increased lung pathology. We also characterised both the humoral and cellular immune responses to infection in both models. The comparability of these data supports the Golden Syrian hamster model being useful in preclinical evaluation studies to explore the efficacy of countermeasures against influenza.

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Impact of Reinfection with SARS-CoV-2 Omicron Variants in Previously Infected Hamsters

Abstract: The emergence of SARS-CoV-2 variants and the widespread use of COVID-19 vaccines has resulted in individual differences in immune status against SARS-CoV-2. A decay in immunity over time and the emergence of variants that partially evade the immune response can also lead to reinfection.

Cited by 5 publications

References 61 publications

Omicron breakthrough infections in vaccinated or previously infected hamsters

Omicron breakthrough infections in vaccinated or previously infected hamsters

Signatures of Original Antigenic Sin or protection following coronavirus imprinting in Syrian hamsters challenged with SARS-CoV-2 or variants

Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters

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