A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Animals
2.3. Experimental Design, Vaccination
2.4. Challenge and Sample Collection
2.5. Virus Titration of Nasal Swabs and BALF
2.6. Pathology
2.7. HI Assay
2.8. ELISA
2.9. Immune Cell Isolation
2.10. IFNγ ELISpot
2.11. Intracellular Cytokine Staining (ICS) and Flow Cytometry
2.12. Statistical Analyses
3. Results
3.1. Vaccination Did Not Result in an Increase of Antibodies against H1 HA Head and Stalk Domains
3.2. Virus Replication in the Respiratory Tract
3.3. Pathology
3.4. Cellular Responses Measured after Challenge Reflect Priming by Influenza Virus Vaccination
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BALF | bronchio-alveolar lavage fluid |
cHA | chimeric hemagglutinin |
CPE | cytophathic effect |
DPC | days post challenge |
Emul | Emulsigen adjuvant |
H&E staining | hematoxylin and eosin staining |
HA | hemagglutinin |
HI | hemagglutination inhibition |
ICS | intracellular cytokine staining |
IFN | interferon |
Ig | immunoglobulin |
IHC | immunohistochemistry |
IIV | inactivated whole virus influenza vaccine |
LAIV | live attenuated influenza virus vaccine |
MDCK | Madin Darby canine kidney |
MEM | minimal essential medium |
NP | nucleoprotein |
PBMCs | peripheral blood mononuclear cells |
PFU | Plaque forming units |
TCID50 | tissue culture infectious dose 50 |
TIV | trivalent inactivated virus vaccine |
TPCK | tosyl phenylalanyl chloromethyl ketone |
VAERD | vaccine-associated enhanced respiratory disease |
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Group | Vaccine Composition | No. of Pigs | ||
---|---|---|---|---|
Prime | Vaccine #1 | Vaccine #2 | ||
G1 | B-cH9/1 a | IIV cH8/1 b | IIV cH5/1 d | 3 |
G1 Emul | B-cH9/1 | IIV cH8/1 with adjuvant | IIV cH5/1 with adjuvant | 3 |
G2 | B-cH9/1 | LAIV cH8/1 c | IIV cH5/1 | 3 |
G2 Emul | B-cH9/1 | LAIV cH8/1 | IIV cH5/1 with adjuvant | 3 |
G3 | - | H1N2 inactivated whole virus with adjuvant | 6 | |
G4 | - | TIV containing H1N1 with adjuvant | 6 | |
C-Cont | Challenged control | 3 | ||
Mock | Non-vaccine & non-challenge (Mock) | 2 |
Parameter | HP Score | ||||
---|---|---|---|---|---|
0 | 1 | 2 | 3 | 4 | |
Lung % involvement: Epithelial changes and inflammation | None | 1–25% | 26–50% | 51–75% | Greater than 75% |
Peribronchiolar cuffing by lymphocytes | None | Mild, loosely formed cuffs of lymphocytes | Moderate, well-formed cuffs of lymphocytes | Prominent thick well-formed cuffs of lymphocytes | |
Degree of interstitial pneumonia (IP) | None | Mild, focal to multifocal IP | Moderate, locally extensive to multifocal IP | Moderate, multifocal to coalescing IP | Severe, coalescing to diffuse IP |
Tracheal epithelial changes & Nasal cavity epithelial changes | None | Early epithelial changes with focal to multifocal loss of cilia and epithelial degenerative changes | Mild epithelial flattening with loss of cilia and goblet cells | Moderate epithelial flattening with decreased thickness of respiratory epithelium, loss of cilia and goblet cells | Flattened epithelium with areas of mucosa covered by a single layer of cuboidal epithelium and epithelial loss (necrosis) |
Degree of rhinitis | None | Mild | Moderate | Severe | |
Degree of tracheitis | None | Mild | Moderate | Severe |
DPC | G1 | G1 Emul | G2 | G2 Emul | G3 | G4 | C-Cont | Mock | |
---|---|---|---|---|---|---|---|---|---|
Vaccine Composition | B virus | B virus | B virus | B virus | |||||
IIV | IIV Emul | LAIV | LAIV | VAERD | TIV | ||||
IIV | IIV Emul | IIV | IIV Emul | ||||||
Nasal swab | 0 | 0/3 | 0/3 | 0/3 | 0/3 | 0/6 | 0/6 | 0/3 | 0/2 |
1 | 0/3 | 0/3 | 0/3 | 0/3 | 0/6 | 0/6 | 0/3 | 0/2 | |
3 | 3/3 | 3/3 | 3/3 | 1/3 | 3/6 | 5/6 | 1/3 | 0/2 | |
5 | 2/3 | 3/3 | 1/3 | 3/3 | 6/6 | 6/6 | 3/3 | 0/2 | |
BALF | 5 | 0/3 | 0/3 | 0/3 | 0/3 | 4/6 | 2/6 | 3/3 | 0/2 |
Experimental Groups | Immunohistochemistry (IHC): Positive/Total Samples | |||||||
---|---|---|---|---|---|---|---|---|
G1 | G1 Emul | G2 | G2 Emul | G3 | G4 | C-Cont | Mock | |
Lung | 2/3 | 3/3 | 2/3 | 2/3 | 6/6 | 6/6 | 1/3 | 0/2 |
Trachea | 0/3 | 2/3 | 2/3 | 3/3 | 6/6 | 5/6 | 3/3 | 0/2 |
Nasal turbinates | 0/3 | 2/3 | 0/3 | 1/3 | 3/6 | 4/6 | 1/3 | 0/2 |
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Sunwoo, S.-Y.; Schotsaert, M.; Morozov, I.; Davis, A.S.; Li, Y.; Lee, J.; McDowell, C.; Meade, P.; Nachbagauer, R.; García-Sastre, A.; et al. A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies. Vaccines 2018, 6, 64. https://doi.org/10.3390/vaccines6030064
Sunwoo S-Y, Schotsaert M, Morozov I, Davis AS, Li Y, Lee J, McDowell C, Meade P, Nachbagauer R, García-Sastre A, et al. A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies. Vaccines. 2018; 6(3):64. https://doi.org/10.3390/vaccines6030064
Chicago/Turabian StyleSunwoo, Sun-Young, Michael Schotsaert, Igor Morozov, Anne Sally Davis, Yuhao Li, Jinhwa Lee, Chester McDowell, Philip Meade, Raffael Nachbagauer, Adolfo García-Sastre, and et al. 2018. "A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies" Vaccines 6, no. 3: 64. https://doi.org/10.3390/vaccines6030064
APA StyleSunwoo, S. -Y., Schotsaert, M., Morozov, I., Davis, A. S., Li, Y., Lee, J., McDowell, C., Meade, P., Nachbagauer, R., García-Sastre, A., Ma, W., Krammer, F., & Richt, J. A. (2018). A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies. Vaccines, 6(3), 64. https://doi.org/10.3390/vaccines6030064