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A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin
A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 204(2)
- Publication Year :
- 2019
-
Abstract
- Computationally optimized broadly reactive Ags (COBRA) targeting H1 elicit a broad cross-reactive and cross-neutralizing Ab response against multiple H1N1 viral strains. To assess B cell breadth, Mus musculus (BALB/c) Ab-secreting cells elicited by a candidate COBRA hemagglutinin (HA) (termed P1) were compared with Ab-secreting cells elicited by historical H1N1 vaccine strains. In addition, to evaluate the Ab response elicited by P1 HA at increased resolution, a panel of P1 HA-specific B cell hybridomas was generated following immunization of mice with COBRA P1 and the corresponding purified mAbs were characterized for Ag specificity and neutralization activity. Both head- and stem-directed mAbs were elicited by the P1 HA Ag, with some mAbs endowed with Ab-dependent cell-mediated cytotoxicity activity. P1 HA-elicited mAbs exhibited a wide breadth of HA recognition, ranging from narrowly reactive to broadly reactive mAbs. Interestingly, we identified a P1 HA-elicited mAb (1F8) exhibiting broad hemagglutination inhibition activity against both seasonal and pandemic H1N1 influenza strains. Furthermore, mAb 1F8 recognized an overlapping, but distinct, epitope compared with other narrowly hemagglutination inhibition–positive mAbs elicited by the P1 or wild-type HA Ags. Finally, P1 HA-elicited mAbs were encoded by distinct H chain variable and L chain variable gene segment rearrangements and possessed unique CDR3 sequences. Collectively, the functional characterization of P1 HA-elicited mAbs sheds further insights into the underlying mechanism(s) of expanded Ab breadth elicited by a COBRA HA-based immunogen and advances efforts toward design and implementation of a more broadly protective influenza vaccine.
- Subjects :
- Immunogen
Hemagglutination
Immunology
Hemagglutinin (influenza)
Hemagglutinin Glycoproteins, Influenza Virus
medicine.disease_cause
Antibodies, Viral
Epitope
Madin Darby Canine Kidney Cells
03 medical and health sciences
Mice
0302 clinical medicine
Dogs
Influenza A Virus, H1N1 Subtype
Antigen
Orthomyxoviridae Infections
Influenza, Human
Influenza A virus
medicine
Immunology and Allergy
Animals
Humans
Mice, Inbred BALB C
Hemagglutination assay
biology
Antibodies, Monoclonal
Computational Biology
Virology
Epitope mapping
Influenza Vaccines
biology.protein
Epitopes, B-Lymphocyte
Female
Broadly Neutralizing Antibodies
Epitope Mapping
030215 immunology
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 204
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....d32c8b2b7e3519d2253cf179dc3296aa