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Human Vaccines & Immunotherapeutics Volume 20, 2024 - Issue 1
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Novel Vaccines

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

Shiyang Maa Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Fei Zhua Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Yizhong Xua Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Haicheng Wene National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
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Mingjun Raoa Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Peipei Zhanga Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Wenzhong Penga Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Yanhui Cuia Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Hang Yanga Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaView further author information
,
Caixia Tanf Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, ChinaView further author information
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Jie Chena Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaCorrespondence[email protected]
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Pinhua Pana Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China;b Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China;c Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China;d Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China;e National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, ChinaCorrespondence[email protected]
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Article: 2293300 | Received 15 Sep 2023, Accepted 06 Dec 2023, Published online: 03 Jan 2024

Figures & data

Figure 1. Graphical abstract.

Figure 1. Graphical abstract.

Table 1. Screen of CTL epitopes.

Table 2. Screen of HTL epitopes.

Table 3. Screen of LBL epitopes.

Figure 2. Prediction of secondary structure of vaccine.

(a) h for alpha helix, e for extended strand, c for random coil (b) percentage of second structure in vaccine sequence (c) blue for alpha helix, red for extended strand and purple for random coil.
Figure 2. Prediction of secondary structure of vaccine.

Figure 3. Construction of multi-epitope vaccine.

(a) 3D structure of the vaccine (b) Protein sequence of the vaccine construction, β-defensin is lighted in red, PADRE sequence in yellow, HTL epitopes are lighted in blue, CTL epitopes in green and B epitopes are lighted in purple, Pam2Cys sequence is lighted in light blue, all the linkers are in black color (c) Ramachandran plot of the vaccine structure (d) Z-score of the vaccine structure
Figure 3. Construction of multi-epitope vaccine.

Figure 4. Docking analysis of vaccine-TLR2 complex, the docking result is on the left, and the analysis of the interactions inside the complex are on the right.

Figure 4. Docking analysis of vaccine-TLR2 complex, the docking result is on the left, and the analysis of the interactions inside the complex are on the right.

Figure 5. Docking analysis of vaccine-TLR4 complex, the docking result is on the left, and the analysis of the interactions inside the complex are on the right.

Figure 5. Docking analysis of vaccine-TLR4 complex, the docking result is on the left, and the analysis of the interactions inside the complex are on the right.

Table 4. Docking analysis of vaccine–TLR combination.

Figure 6. The results of molecular dynamics simulation.

(a) RMSD (root mean square deviation) plots of vaccine−TLRs, reflect the stability between the vaccine and TLR-2, TLR-4 receptor. (b) Radius of gyration (Rg) of vaccine-TLRs, suggesting the compactness of complexes (c, d) RMSF (root mean square fluctuation) of vaccine−TLRs, reflects the flexibility and fluctuation of the amino-acids residues in the side chain of docked complex Vaccine−TLR2(c), and TLR4(d). (e) H-bonds formed in complexes
Figure 6. The results of molecular dynamics simulation.

Table 5. MMPBSA of vaccine-TLR2/TLR4 delta (complex - receptor - ligand).

Figure 7. Immune simulation after 3 doses of vaccination.

(a). Antibody levels induced by three doses of vaccine injection. (b) Population of B cells induced. (c) Levels of plasma B cells induced. (d) Population of helper T(TH) cells (e) Population of TH cells per state (f) Population of cytotoxic T(TC) cells induced (g) Population of Nature killer (NK) cells (h) Population of Macrophage (MA) cells (i) Levels of cytokines induced.
Figure 7. Immune simulation after 3 doses of vaccination.

Figure 8. Population coverage of the vaccine.

Figure 8. Population coverage of the vaccine.

Figure 9. In silico cloning of codon-optimized vaccine into E. coli K12’s expression system.

Figure 9. In silico cloning of codon-optimized vaccine into E. coli K12’s expression system.
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