Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global va...

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Main Authors: Ki-Hye Kim, Noopur Bhatnagar, Subbiah Jeeva, Judy Oh, Bo Ryoung Park, Chong Hyun Shin, Bao-Zhong Wang, Sang-Moo Kang
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/4/316
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spelling doaj-8acbbb28d674473f8d668fa75cdc092d2021-03-29T23:04:06ZengMDPI AGVaccines2076-393X2021-03-01931631610.3390/vaccines9040316Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged MiceKi-Hye Kim0Noopur Bhatnagar1Subbiah Jeeva2Judy Oh3Bo Ryoung Park4Chong Hyun Shin5Bao-Zhong Wang6Sang-Moo Kang7Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USACenter for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30302, USASevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global vaccination program. The efficacy of many different versions of vaccine candidates and adjuvant effects remain unknown, particularly in the elderly. In this study, we compared the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain in young adult and aged mice, S1 with receptor binding domain, and S2 with fusion domain. Full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Old-aged mice induced SARS-CoV-2 spike-specific IgG antibodies with neutralizing activity after high dose S vaccination. With an increased vaccine dose, S1 was highly effective in inducing neutralizing and receptor-binding inhibiting antibodies, although both S1 and S2 subunit domain vaccines were similarly immunogenic. Adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses. Results of this study provide information in designing SARS-CoV-2 spike vaccine antigens and effective vaccination in the elderly.https://www.mdpi.com/2076-393X/9/4/316SARS-CoV-2spikeneutralizing activityRBD-hACE2 inhibitioncellular immunityaged mice
collection DOAJ
language English
format Article
sources DOAJ
author Ki-Hye Kim
Noopur Bhatnagar
Subbiah Jeeva
Judy Oh
Bo Ryoung Park
Chong Hyun Shin
Bao-Zhong Wang
Sang-Moo Kang
spellingShingle Ki-Hye Kim
Noopur Bhatnagar
Subbiah Jeeva
Judy Oh
Bo Ryoung Park
Chong Hyun Shin
Bao-Zhong Wang
Sang-Moo Kang
Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
Vaccines
SARS-CoV-2
spike
neutralizing activity
RBD-hACE2 inhibition
cellular immunity
aged mice
author_facet Ki-Hye Kim
Noopur Bhatnagar
Subbiah Jeeva
Judy Oh
Bo Ryoung Park
Chong Hyun Shin
Bao-Zhong Wang
Sang-Moo Kang
author_sort Ki-Hye Kim
title Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
title_short Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
title_full Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
title_fullStr Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
title_full_unstemmed Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice
title_sort immunogenicity and neutralizing activity comparison of sars-cov-2 spike full-length and subunit domain proteins in young adult and old-aged mice
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2021-03-01
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be expanding the pandemic disease across the globe. Although SARS-CoV-2 vaccines were rapidly developed and approved for emergency use of vaccination in humans, supply and production difficulties are slowing down the global vaccination program. The efficacy of many different versions of vaccine candidates and adjuvant effects remain unknown, particularly in the elderly. In this study, we compared the immunogenic properties of SARS-CoV-2 full-length spike (S) ectodomain in young adult and aged mice, S1 with receptor binding domain, and S2 with fusion domain. Full-length S was more immunogenic and effective in inducing IgG antibodies after low dose vaccination, compared to the S1 subunit. Old-aged mice induced SARS-CoV-2 spike-specific IgG antibodies with neutralizing activity after high dose S vaccination. With an increased vaccine dose, S1 was highly effective in inducing neutralizing and receptor-binding inhibiting antibodies, although both S1 and S2 subunit domain vaccines were similarly immunogenic. Adjuvant effects were significant for effective induction of IgG1 and IgG2a isotypes, neutralizing and receptor-binding inhibiting antibodies, and antibody-secreting B cell and interferon-γ secreting T cell immune responses. Results of this study provide information in designing SARS-CoV-2 spike vaccine antigens and effective vaccination in the elderly.
topic SARS-CoV-2
spike
neutralizing activity
RBD-hACE2 inhibition
cellular immunity
aged mice
url https://www.mdpi.com/2076-393X/9/4/316
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