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Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.

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Title: Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.
Authors: Stoddard, Madison, Yuan, Lin, Sarkar, Sharanya, Mangalaganesh, Shruthi, Nolan, Ryan P., Bottino, Dean, Hather, Greg, Hochberg, Natasha S., White, Laura F., Chakravarty, Arijit
Source: Vaccines; Apr2023, Vol. 11 Issue 4, p806, 14p
Subject Terms: SARS-CoV-2, BOOSTER vaccines, HETEROGENEITY, BINDING site assay, IMMUNITY
Abstract: SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals. [ABSTRACT FROM AUTHOR]
Copyright of Vaccines is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
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  Data: Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.
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  Data: <searchLink fieldCode="AR" term="%22Stoddard%2C+Madison%22">Stoddard, Madison</searchLink><br /><searchLink fieldCode="AR" term="%22Yuan%2C+Lin%22">Yuan, Lin</searchLink><br /><searchLink fieldCode="AR" term="%22Sarkar%2C+Sharanya%22">Sarkar, Sharanya</searchLink><br /><searchLink fieldCode="AR" term="%22Mangalaganesh%2C+Shruthi%22">Mangalaganesh, Shruthi</searchLink><br /><searchLink fieldCode="AR" term="%22Nolan%2C+Ryan+P%2E%22">Nolan, Ryan P.</searchLink><br /><searchLink fieldCode="AR" term="%22Bottino%2C+Dean%22">Bottino, Dean</searchLink><br /><searchLink fieldCode="AR" term="%22Hather%2C+Greg%22">Hather, Greg</searchLink><br /><searchLink fieldCode="AR" term="%22Hochberg%2C+Natasha+S%2E%22">Hochberg, Natasha S.</searchLink><br /><searchLink fieldCode="AR" term="%22White%2C+Laura+F%2E%22">White, Laura F.</searchLink><br /><searchLink fieldCode="AR" term="%22Chakravarty%2C+Arijit%22">Chakravarty, Arijit</searchLink>
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  Data: Vaccines; Apr2023, Vol. 11 Issue 4, p806, 14p
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  Data: <searchLink fieldCode="DE" term="%22SARS-CoV-2%22">SARS-CoV-2</searchLink><br /><searchLink fieldCode="DE" term="%22BOOSTER+vaccines%22">BOOSTER vaccines</searchLink><br /><searchLink fieldCode="DE" term="%22HETEROGENEITY%22">HETEROGENEITY</searchLink><br /><searchLink fieldCode="DE" term="%22BINDING+site+assay%22">BINDING site assay</searchLink><br /><searchLink fieldCode="DE" term="%22IMMUNITY%22">IMMUNITY</searchLink>
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  Label: Abstract
  Group: Ab
  Data: SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of Vaccines is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/vaccines11040806
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        Text: English
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        PageCount: 14
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        Type: general
      – SubjectFull: BOOSTER vaccines
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      – SubjectFull: HETEROGENEITY
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      – SubjectFull: BINDING site assay
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              Text: Apr2023
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              Y: 2023
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