Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19

Gregory, David J.; Vannier, Augustin; Duey, Akiro H.; Roady, Tyler J; Dzeng, Richard K.; Pavlovic, Maia; Chapin, Michael H; Mukherjee, Sonia; Wilmot, Hannah; Chronos, Nic; Charles, Richelle C.; Ryan, Edward T.; LaRocque, Regina C.; Miller, Tyler E.; García-Beltrán, Wilfredo F.; Thierauf, Julia; Iafrate, A. John; Mullenbrock, Steven; Stump, Mark; Wetzel, Randall K.; Polakiewicz, Roberto D.; Naranbhai, Vivek; Poznansky, Mark C.

doi:10.1080/21505594.2022.2073025

Cited by 14 publications

(13 citation statements)

References 46 publications

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“…HCoV-OC43 and HCoV-HKU1 have been used to model postpandemic SARS-CoV-2 transmission ( 32 ) to predict annual seasonal peaks with immune duration of 40 weeks for SARS CoV-2. Duration of immunity to SARS-CoV-2 varies by natural infection ( 39 ), disease severity ( 72 ), and vaccine type ( 63 ), with evidence for cumulative protection achieved by both natural infection and vaccination ( 63 ). While repeated natural infection plays an important role in achieving endemic stability, prior immunity is essential to limit morbidity.…”

Section: Discussionmentioning

confidence: 99%

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

Mullin¹,

Wyk

Asher

et al. 2022

PNAS Nexus

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The contours of endemic coronaviral disease in humans and other animals are shaped by the tendency of coronaviruses to generate new variants superimposed upon non-sterilizing immunity. Consequently, patterns of coronaviral reinfection in animals can inform the emerging endemic state of the SARS-CoV-2 pandemic. We generated controlled reinfection data after high and low risk natural exposure or heterologous vaccination to sialodacryoadenitis (SDAV) in rats. Using deterministic compartmental models, we utilized in vivo estimates from these experiments to model the combined effects of variable transmission rates, variable duration of immunity, successive waves of variants and vaccination on patterns of viral transmission. Using rat experiment-derived estimates, an endemic state achieved by natural infection alone occurred after a median of 724 days with approximately 41.3% of the population susceptible to reinfection. After accounting for translationally altered parameters between rat-derived data and human SARS-CoV-2 transmission, and after introducing vaccination, we arrived at a median time to endemic stability of 1437 (IQR = 749.25) days with a median 15.4% of the population remaining susceptible. We extended the models to introduce successive variants with increasing transmissibility and included the effect of varying duration of immunity. As seen with endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. However, vaccination combined with natural immunity maintains a lower prevalence of infection than natural infection alone and provides greater resilience against the effects of transmissible variants. Significance Statement The pandemic to endemic trajectory of SARS-CoV-2 transmission will be shaped by the tendency of coronaviruses to elicit non-sterilizing immunity and generate new variants. We utilized estimates from controlled rat coronaviral infection in deterministic compartmental models to inform routes to endemic stability in SARS-CoV-2. We introduced translationally altered parameters to explore the effects of waning immunity, exposure to increasingly transmissible variants and successive vaccination. We arrived at an endemic state in which 15% of the population remains susceptible to reinfection. Similar to endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. Accumulating and maintaining evolving immunity through vaccination and inevitable natural exposure is essential to achieving a stable endemic state.

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Section: Discussionmentioning

confidence: 99%

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

Mullin¹,

Wyk

Asher

et al. 2022

PNAS Nexus

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…In response to human coronaviruses, neutralizing antibodies typically bind to the S protein and disrupt viral entry by blocking interactions between viruses and ACE2 host receptors [11]. However, N proteins from different viruses used as vaccines can protect the hosts against the virus infections [11]. Severe infection was associated with enhanced anti-S and anti-N protein antibody responses, and high anti-N protein titers were especially observed in patients who suffered long hospitalizations.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection

Delgado

Vidal-Pla

Moya

et al. 2022

Journal of Immunology Research

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Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively ( p = 0.005 ). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.

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“…The most typical clinical manifestations are shortness of breath and dyspnea, or conscious disturbance, lethargy, dehydration, loss of appetite, etc. 17 The fundamental aspect to the treatment of pneumonia is to find out the cause; if it is infectious pneumonia, then anti-infection treatment should be prescribed as a priority. 18 If pneumonia is caused by immune damage, then the immune system should be alleviated.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A induces protective autophagy to alleviate inflammation, oxidative stress, and endoplasmic reticulum stress in pediatric pneumonia

Cao

Wang

Wan

2022

Allergol Immunopathol

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Objective: To investigate the therapeutic effect of urolithin A (UA) on pediatric pneumonia and the underlying mechanisms. Methods: The pediatric infantile pneumonia model was constructed by intratracheal induction of lipopolysaccharide (LPS) in 1-week-old C57BL/6 mice (male, 4–5 g). UA was also injected intraperitoneally. Lung tissues in each group were examined by histological analysis. Autophagy, inflammation, and oxidative stress were assessed by enzyme-linked-immunosorbent serologic assay and immunoblot analysis. Moreover, pyrophosis and endoplasmic reticulum stress were also evaluated by immunoblot analysis. Results: UA alleviated lung inflammation in mice, and inhibited cell pyrophosis. In addition, UA A relieved both oxidative and endoplasmic reticulum stress. Furthermore, we found that UA alleviated pneumonia damage by inducing protective autophagy. Conclusion: UA induced protective autophagy to alleviate inflammation, oxidative stress, and endoplasmic reticulum stress in pediatric pneumonia.

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Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19

Cited by 14 publications

References 46 publications

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

SARS-CoV-2 Spike Protein Vaccine-Induced Immune Imprinting Reduces Nucleocapsid Protein Antibody Response in SARS-CoV-2 Infection

Urolithin A induces protective autophagy to alleviate inflammation, oxidative stress, and endoplasmic reticulum stress in pediatric pneumonia

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