Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Recombinant Antigen Production
2.2. Calf Husbandry and Field Site
2.3. Immunisation Strategy
2.3.1. Immunogenicity Trial
2.3.2. Vaccine Efficacy Trial
2.4. Natural Exposure to O. ochengi
2.5. Routine Sampling and Clinical Observations
2.6. End-Point Sampling
2.7. Entomological Analyses and Transmission Potential
2.8. Measuring Anti-Ov-103 and Ov-Ral-2 IgG Responses
2.9. IgG Purification and Epitope Mapping
2.10. Protein Structure Prediction
2.11. PBMC Proliferation Assays
2.12. Statistical Data Analysis
2.12.1. Immunisation Period
2.12.2. Exposure Period
2.12.3. Assessing Immunological Correlates of Vaccine-Associated Protection
2.12.4. Final Parasitological Burden
3. Results
3.1. Ov-103 and Ov-RAL-2 Immunisation in Cattle with MontanideTM ISA 206VG Induces Pronounced, Rapid and Sustained Seroconversion
3.2. Ov-103 and Ov-RAL-2 Immunisation in Cattle Is Associated with Reduced O. ochengi Female and Microfilarial Worm Burdens following Natural Exposure
3.3. Vaccine-Induced Ov-103 and Ov-RAL-2-Specific Serum IgG Responses Are Associated with Reduced Adult O. ochengi Burdens following Natural Exposure
3.4. Epitope Mapping Identifies Immunogenic Surface Peptide Sequences of Ov-103 and Ov-RAL-2
3.5. Ov-103 and Ov-RAL-2 Immunisation in Cattle Is Associated with Altered Cellular Immune Responses
3.6. Calf Health and Diagnostics
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | ID | Ov-RAL-2 | Ov-103 | ||||
---|---|---|---|---|---|---|---|
IgG | IgG1 | IgG2 | IgG | IgG1 | IgG2 | ||
Control | 2901 | 5800 | 0 | 0 | 2300 | 0 | 0 |
2904 | 0 | 0 | 0 | 0 | 0 | 0 | |
2911 | 0 | 0 | 0 | 900 | 0 | 0 | |
Rehydragel | 2906 | 47,700 | 15,800 | 0 | 19,500 | 34,200 | 0 |
2908 | 18,300 | 15,100 | 0 | 9500 | 47,700 | 0 | |
Advax-2 | 2910 | 12,800 | 11,900 | 0 | 5000 | 38,800 | 0 |
2912 | 24,000 | 28,300 | 0 | 8500 | 44,300 | 0 | |
Montanide | 2907 | 944,300 | 669,900 | 1,086,800 | 373,900 | 233,300 | 27,300 |
2909 | 1,039,700 | 87,700 | 868,200 | 283,200 | 82,200 | 721,200 | |
2913 | 404,000 | 524,000 | 119,900 | 216,500 | 183,200 | 28,200 |
Control Group (n = 11) | Vaccine Group (n = 10) | |
---|---|---|
Nodule burden | 20.2 (±21.0); 3–79 | 13.2 (±13.6); 2–43 |
Nodule diameter (mm) | 4.8 (0.8); 3.1–7.8 (nodules assessed = 147) | 4.7 (0.8); 3.0–7.0 (nodules assessed = 107) |
Nodule age * (days) | 545 (±89); 293–694 (nodules assessed = 147) | 536 (±101); 266–688 (nodules assessed = 107) |
Nodule weight (mg) | 100.6 (45.6); 22.7–269.4 (nodules assessed = 128) | 88.6 (40.3); 24.6–250.1 (nodules assessed = 100) |
Male worms recovered per nodule | 0.5 (0.7); 0–3 (nodules assessed = 50) | 0.7 (1.2); 0–5 (nodules assessed = 38) |
O. ochengi microfilarial density (per mg skin) | 4.7 (±7.9); 0–25.1 | 1.4 (±1.6); 0–4.5 |
Response Variable (Y) | Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
---|---|---|---|---|
Female worm nodules | Time | 0.024 | 0.0017 | <0.0001 * |
Sex (m) | 2.65 | 1.72 | 0.14 | |
Vaccination:Time (interaction) | −0.0062 | 0.0022 | 0.0043 * | |
Microfilarial burden | Time | 0.0080 | 0.0012 | <0.0001 * |
Sex (m) | 0.76 | 0.78 | 0.34 | |
Vaccination:Time (interaction) | −0.0031 | 0.0012 | 0.0085 * |
Anti-Ov-103 IgG Responses | ||||
---|---|---|---|---|
Response Variable (Y) | Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | Time | −0.00013 | 0.00038 | 0.74 |
Sex (m) | 0.025 | 0.056 | 0.66 | |
Vaccination:Time (interaction) | 0.0091 | 0.00051 | <0.0001 * | |
IgG1 titre (logged) | Time | −0.013 | 0.0091 | 0.15 |
Sex (m) | −0.15 | 0.43 | 0.74 | |
Vaccination:Time (interaction) | 0.21 | 0.0090 | <0.0001 * | |
IgG2 titre (logged) | Time | −0.016 | 0.011 | 0.17 |
Sex (m) | −0.29 | 0.97 | 0.77 | |
Vaccination:Time (interaction) | 0.16 | 0.014 | <0.0001 * | |
Anti-Ov-RAL-2 IgG Responses | ||||
Response Variable (Y) | Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | Time | −0.00020 | 0.00041 | 0.62 |
Sex (m) | 0.039 | 0.059 | 0.52 | |
Vaccination:Time (interaction) | 0.0083 | 0.00055 | <0.0001 * | |
IgG1 titre (logged) | Time | −0.018 | 0.010 | 0.094 |
Sex (m) | 0.19 | 0.49 | 0.70 | |
Vaccination:Time (interaction) | 0.21 | 0.010 | <0.0001 * | |
IgG2 titre (logged) | Time | −0.0075 | 0.011 | 0.50 |
Sex (m) | −0.13 | 0.71 | 0.85 | |
Vaccination:Time (interaction) | 0.15 | 0.013 | <0.0001 * |
Anti-Ov-103 IgG Responses | ||||
---|---|---|---|---|
Response Variable (Y) | Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | Time | 0.000031 | 0.000029 | 0.30 |
Vaccination | 0.51 | 0.056 | <0.0001 * | |
Sex (m) | −0.013 | 0.058 | 0.82 | |
Vaccination:Time (interaction) | −0.00062 | 0.000042 | <0.0001 * | |
IgG1 titre (logged) | Time | 0.0040 | 0.0020 | 0.053 |
Vaccination | 12.21 | 1.17 | <0.0001 * | |
Sex (m) | 0.69 | 0.87 | 0.44 | |
Vaccination:Time (interaction) | −0.017 | 0.0029 | <0.0001 * | |
IgG2 titre (logged) | Time | 0.0025 | 0.0019 | 0.19 |
Vaccination | 8.34 | 1.46 | <0.0001 * | |
Sex (m) | −0.56 | 1.34 | 0.68 | |
Vaccination:Time (interaction) | −0.010 | 0.0027 | 0.00054 * | |
Anti-Ov-RAL-2 IgG Responses | ||||
Response Variable (Y) | Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | Time | 0.000050 | 0.000031 | 0.10 |
Vaccination | 0.43 | 0.043 | <0.0001 * | |
Sex (m) | 0.047 | 0.042 | 0.28 | |
Vaccination:Time (interaction) | −0.00055 | 0.000044 | <0.0001 * | |
IgG1 titre (logged) | Time | 0.0052 | 0.0017 | 0.0042 * |
Vaccination | 12.68 | 1.04 | <0.0001 * | |
Sex (m) | 1.51 | 0.81 | 0.076 | |
Vaccination:Time (interaction) | −0.016 | 0.0025 | <0.0001 * | |
IgG2 titre (logged) | Time | 0.0039 | 0.0016 | 0.020 * |
Vaccination | 8.62 | 1.37 | <0.0001 * | |
Sex (m) | −0.97 | 1.31 | 0.46 | |
Vaccination:Time (interaction) | −0.011 | 0.0023 | <0.0001 * |
Anti-Ov-103 IgG Responses | |||
---|---|---|---|
Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | −8.01 | 1.83 | <0.0001 * |
Sex (m) | 2.62 | 2.74 | 0.36 |
Total IgG:Time (interaction) | 0.034 | 0.0059 | <0.0001 * |
IgG1 titre (logged) | −0.52 | 0.17 | 0.0059 * |
Sex (m) | 1.51 | 1.58 | 0.36 |
IgG1 titre (logged):Time (interaction) | 0.0012 | 0.00045 | 0.015 * |
IgG2 titre (logged) | −0.38 | 0.18 | 0.046 * |
Sex (m) | 1.42 | 1.75 | 0.43 |
IgG2 titre (logged):Time (interaction) | 0.00095 | 0.00051 | 0.073 |
Anti-Ov-RAL-2 IgG Responses | |||
Fixed-Effect Explanatory Variable (x) | Co-Efficient Value (β) | Standard Error | p-Value |
Total IgG | −7.40 | 1.83 | <0.0001 * |
Sex (m) | 0.42 | 2.94 | 0.89 |
Total IgG:Time (interaction) | 0.049 | 0.0050 | <0.0001 * |
IgG1 titre (logged) | −0.55 | 0.18 | 0.0057 * |
Sex (m) | 1.66 | 1.61 | 0.33 |
IgG1 titre (logged):Time (interaction) | 0.00094 | 0.00038 | 0.023 * |
IgG2 titre (logged) | −0.40 | 0.19 | 0.043 * |
Sex (m) | 1.08 | 1.75 | 0.55 |
IgG2 titre (logged):Time (interaction) | 0.0011 | 0.00052 | 0.044 * |
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Luu, L.; Bah, G.S.; Okah-Nnane, N.H.; Hartley, C.S.; Glover, A.F.; Walsh, T.R.; Lian, L.-Y.; Zhan, B.; Bottazzi, M.E.; Abraham, D.; Petrovsky, N.; Bayang, N.; Tangwa, B.; Ayiseh, R.B.; Mbah, G.E.; Ekale, D.D.; Tanya, V.N.; Lustigman, S.; Makepeace, B.L.; Graham-Brown, J. Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis. Vaccines 2022, 10, 861. https://doi.org/10.3390/vaccines10060861
Luu L, Bah GS, Okah-Nnane NH, Hartley CS, Glover AF, Walsh TR, Lian L-Y, Zhan B, Bottazzi ME, Abraham D, Petrovsky N, Bayang N, Tangwa B, Ayiseh RB, Mbah GE, Ekale DD, Tanya VN, Lustigman S, Makepeace BL, Graham-Brown J. Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis. Vaccines. 2022; 10(6):861. https://doi.org/10.3390/vaccines10060861
Chicago/Turabian StyleLuu, Lisa, Germanus S. Bah, Ndode Herman Okah-Nnane, Catherine S. Hartley, Alexandra F. Glover, Tessa R. Walsh, Lu-Yun Lian, Bin Zhan, Maria Elena Bottazzi, David Abraham, Nikolai Petrovsky, Nicolas Bayang, Bernard Tangwa, Rene Billingwe Ayiseh, Glory Enjong Mbah, David D. Ekale, Vincent N. Tanya, Sara Lustigman, Benjamin L. Makepeace, and John Graham-Brown. 2022. "Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis" Vaccines 10, no. 6: 861. https://doi.org/10.3390/vaccines10060861