دورية أكاديمية
أعرض في EDS

Multi-COBRA hemagglutinin formulated with cGAMP microparticles elicits protective immune responses against influenza viruses.

التفاصيل البيبلوغرافية
العنوان: Multi-COBRA hemagglutinin formulated with cGAMP microparticles elicits protective immune responses against influenza viruses.
المؤلفون: Zhang X; Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, USA., Shi H; Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, USA., Hendy DA; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA., Bachelder EM; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA., Ainslie KM; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina, USA.; Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA., Ross TM; Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, USA.; Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, Florida, USA.; Department of Infection Biology, Lehner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
المصدر: MSphere [mSphere] 2024 Jul 30; Vol. 9 (7), pp. e0016024. Date of Electronic Publication: 2024 Jun 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society for Microbiology, [2015]-
مواضيع طبية MeSH: Adjuvants, Immunologic*/administration & dosage , Antibodies, Viral*/blood , Antibodies, Viral*/immunology , Hemagglutinin Glycoproteins, Influenza Virus*/immunology , Influenza Vaccines*/immunology , Influenza Vaccines*/administration & dosage , Nucleotides, Cyclic*/immunology , Nucleotides, Cyclic*/administration & dosage , Orthomyxoviridae Infections*/prevention & control , Orthomyxoviridae Infections*/immunology, Animals ; Female ; Humans ; Mice ; Mice, Inbred BALB C
مستخلص: In humans, seasonal influenza viruses cause epidemics. Avian influenza viruses are of particular concern because they can infect multiple species and lead to unpredictable and severe disease. Therefore, there is an urgent need for a universal influenza vaccine that provides protection against all influenza strains. The cyclic GMP-AMP (cGAMP) is a promising adjuvant for subunit vaccines, which promotes type I interferons' production through the stimulator of interferon genes (STING) pathway. The encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles (MPs) enhances its intracellular delivery. In this study, the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology was used to generate H1, H3, and H5 vaccine candidates. Monovalent and multivalent COBRA HA vaccines formulated with cGAMP Ace-DEX MPs were evaluated in mice for protective antibody responses. cGAMP MPs adjuvanted COBRA HA vaccines elicited robust antigen-specific antibodies following vaccination. Compared with COBRA HA vaccine groups with no adjuvant or blank MPs, the cGAMP MPs enhanced HAI activity elicited by COBRA HA vaccines. The HAI activity was not significantly different between cGAMP MPs adjuvanted monovalent or multivalent COBRA HA vaccines. The cGAMP MPs adjuvanted COBRA vaccine groups had higher antigen-specific IgG2a-binding titers than the COBRA vaccine groups with no adjuvant or blank MPs. The COBRA vaccines formulated with cGAMP MPs mitigated diseases caused by influenza viral challenge and decreased pulmonary viral titers in mice. Therefore, the formulation of COBRA vaccines plus cGAMP MPs is a promising universal influenza vaccine that elicits protective immune responses against human seasonal and pre-pandemic strains.
Importance: Influenza viruses cause severe respiratory disease, particularly in the very young and the elderly. Next-generation influenza vaccines are needed to protect against new influenza variants. This report used a promising adjuvant, cyclic GMP-AMP (cGAMP), to enhance the elicited antibodies by an improved influenza hemagglutinin candidate and protect against influenza virus infection. Overall, adding adjuvants to influenza vaccines is an effective method to improve vaccines.
Competing Interests: The authors declare no conflict of interest.
التعليقات: Update of: bioRxiv. 2024 Feb 29:2024.02.27.582355. doi: 10.1101/2024.02.27.582355. (PMID: 38464191)
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معلومات مُعتمدة: 75N93019C00052 United States AI NIAID NIH HHS; R01 AI147497 United States AI NIAID NIH HHS; GRA-001 Georgia Research Alliance (GRA)
فهرسة مساهمة: Keywords: COBRA; acetalated-dextran (Ace-DEX); cGAMP; influenza; mice; microparticles (MPs); vaccine
المشرفين على المادة: 0 (Adjuvants, Immunologic)
0 (Antibodies, Viral)
0 (cyclic guanosine monophosphate-adenosine monophosphate)
0 (Hemagglutinin Glycoproteins, Influenza Virus)
0 (Influenza Vaccines)
0 (Nucleotides, Cyclic)
تواريخ الأحداث: Date Created: 20240626 Date Completed: 20240730 Latest Revision: 20240801
رمز التحديث: 20240801
مُعرف محوري في PubMed: PMC11288037
DOI: 10.1128/msphere.00160-24
PMID: 38920382
قاعدة البيانات: MEDLINE
الوصف
تدمد:2379-5042
DOI:10.1128/msphere.00160-24