The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation

Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum)...

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Main Authors: Parakkal Jovvian George, Wanbo Tai, Lanying Du, Sara Lustigman
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/2/251
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spelling doaj-c92539caf2614beaa170fe35220627582020-11-25T03:08:25ZengMDPI AGVaccines2076-393X2020-05-01825125110.3390/vaccines8020251The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant FormulationParakkal Jovvian George0Wanbo Tai1Lanying Du2Sara Lustigman3Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USALaboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USALaboratory of Viral Immunology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USALaboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAVaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.https://www.mdpi.com/2076-393X/8/2/251adjuvantsadjuvant combinationaluminumrASP-1synergyMERS-CoV
collection DOAJ
language English
format Article
sources DOAJ
author Parakkal Jovvian George
Wanbo Tai
Lanying Du
Sara Lustigman
spellingShingle Parakkal Jovvian George
Wanbo Tai
Lanying Du
Sara Lustigman
The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
Vaccines
adjuvants
adjuvant combination
aluminum
rASP-1
synergy
MERS-CoV
author_facet Parakkal Jovvian George
Wanbo Tai
Lanying Du
Sara Lustigman
author_sort Parakkal Jovvian George
title The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
title_short The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
title_full The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
title_fullStr The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
title_full_unstemmed The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation
title_sort potency of an anti-mers coronavirus subunit vaccine depends on a unique combinatorial adjuvant formulation
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2020-05-01
description Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.
topic adjuvants
adjuvant combination
aluminum
rASP-1
synergy
MERS-CoV
url https://www.mdpi.com/2076-393X/8/2/251
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