Recombinant vaccines: Current updates and future prospects

Abstract

Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses. The technology improved vaccine manufacturing, rendering it more efficient and economical. These vaccines have multiple advantages compared to conventional vaccines. The pandemic has heightened awareness of the advantages of these vaccine technologies; trust and acceptance of these vaccines are steadily growing globally. This work offers an overview of the prospects and advantages associated with recombinant vaccines. Additionally, it discusses some of the challenges likely to arise in the future. Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases (especially vector-borne and emerging diseases) and hurdles faced throughout the vaccine development process, especially in enhancing the effectiveness of these vaccines. Moreover, their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects. This review also reviewed the hurdles faced throughout the vaccine development process, especially in enhancing the effectiveness of these vaccines against vector-borne diseases, emerging diseases, and untreatable diseases with high mortality rates like AIDS as well as cancer.

Keywords

Malaria / Dengue / Emerging diseases / Immunoinformatics / Virus-like particles / CRISPR-Cas9

References

[1] Gupta S, Pellett S. Recent developments in vaccine design: From live vaccines to recombinant toxin vaccines. Toxins 2023; 15(9): 563.

[2] Verger P, Dube E. Restoring confidence in vaccines in the COVID-19 era. Expert Rev Vaccines 2020; 19(11): 991-993.

[3] Watson OJ, Barnsley G, Toor J, Hogan AB, Winskill P, Ghani AC. Global impact of the first year of COVID-19 vaccination: A mathematical modelling study. Lancet Infect Dis 2022; 22(9): 1293-1302.

[4] World Health Organization. Number of COVID–19 cases reported to WHO. 2023. [Online]. Available from: https://covid19.who.int. [Accessed on 21 June 2023].

[5] Afrough B, Dowall S, Hewson R. Emerging viruses and current strategies for vaccine intervention. Clin Exp Immunol 2019; 196(2): 157-166.

[6] de Oliveira NR, Santos FDS, dos Santos VAC, Maia MAC, Oliveira TL, Dellagostin OA. Challenges and strategies for developing recombinant vaccines against leptospirosis: Role of expression platforms and adjuvants in achieving protective efficacy. Pathogens 2023; 12(6): 787. https://doi.org/10.3390/pathogens12060787.

[7] Ghattas M, Dwivedi G, Lavertu M, Alameh MG. Vaccine technologies and platforms for infectious diseases: Current progress, challenges, and opportunities. Vaccines 2021; 9(12): 1490. doi: 10.3390/vaccines9121490.

[8] Travieso T, Li J, Mahesh S, Mello JDFRE, Blasi M. The use of viral vectors in vaccine development. NPJ Vaccines 2022; 7(1): 75. doi: 10.1038/s41541-022-00503-y.

[9] Gebre MS, Brito LA, Tostanoski LH, Edwards DK, Carfi A, Barouch DH. Novel approaches for vaccine development. Cell 2021; 184(6): 1589-1603.

[10] Aqib AI, Anjum AA, Islam MA, Murtaza A, Rehman AU. Recent global trends in vaccinology, advances and challenges. Vaccines 2023; 11(3): 520. https://doi.org/10.3390/vaccines11030520.

[11] Yadav T, Srivastava N, Mishra G, Dhama K, Kumar S, Puri B, et al. Recombinant vaccines for COVID-19. Hum Vaccin Immunother 2020; 16(12): 2905-2912.

[12] Wang SY, Liu WQ, Li YQ, Li JX, Zhu FC. A China-developed adenovirus vector-based COVID-19 vaccine: Review of the development and application of Ad5-nCov. Expert Rev Vaccines 2023; 22(1): 704-713.

[13] Wu S, Huang J, Zhang Z, Wu J, Zhang J, Hu H, et al. Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: Preliminary report of an open-label and randomised phase 1 clinical trial. Lancet Infect Dis 2021; 21(12): 1654-1664.

[14] Khandker SS, Godman B, Jawad MI, Meghla BA, Tisha TA, Khondoker MU, et al. A systematic review on COVID-19 vaccine strategies, their effectiveness, and issues. Vaccines (Basel) 2021; 9(12): 1387. doi: 10.3390/vaccines9121387.

[15] Whitaker HJ, Tsang RSM, Byford R, Andrews NJ, Sherlock J, Sebastian Pillai P, et al. Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups. J Infect 2022; 84(5): 675-683.

[16] Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020; 396(10249): 467-478.

[17] Al-Jighefee HT, Najjar H, Ahmed MN, Qush A, Awwad S, Kamareddine L. COVID-19 vaccine platforms: Challenges and safety contemplations. Vaccines (Basel) 2021; 9(10): 1196. doi: 10.3390/vaccines9101196.

[18] Zhang H, Ren J, Li J, Zhai C, Mao F, Yang S, et al. Comparison of heterologous prime-boost immunization strategies with DNA and recombinant vaccinia virus co-expressing GP3 and GP5 of European type porcine reproductive and respiratory syndrome virus in pigs. Microb Pathog 2023; 183: 106328. https://doi.org/10.1016/j.micpath.2023.106328.

[19] Martynova E, Hamza S, Garanina EE, Kabwe E, Markelova M, Shakirova V, et al. Long term immune response produced by the SputnikV vaccine. Int J Mol Sci 2021; 22(20): 11211. doi: 10.3390/ ijms222011211.

[20] Ikegame S, Siddiquey MNA, Hung CT, Haas G, Brambilla L, Oguntuyo KY, et al. Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants. Nat Commun 2021; 12(1): 4598. https://doi.org/10.1038/s41467-021-24909-9.

[21] Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase 1/2 studies from Russia. Lancet 2020; 396(10255): 887-897.

[22] Friedman-Klabanoff DJ, Tjaden A, Santacatterina M, Munawar I, Sanders JW, Herrington DM, et al. 588. Seroconversion among adults after receiving at least one dose of a COVID-19 vaccine: COVID-19 community research partnership, mid-Atlantic, Southeast and Southern United States, December 2020-May 2021. Open Forum Infect Dis 2021; 8(Suppl 1): S396-S397.

[23] Giacaman A, Mir Perelló M, Rodríguez Diez L, Martín-Santiago A. Juvenile dermatomyositis during the SARS-CoV-2 pandemic: Acral and oral mucosal involvement. Adas Dermo–Sifiliográficas 2023; 114(2): T167-T170. https://doi.org/10.1016/j.ad.2022.05.032.

[24] Parums DV. Editorial: First approval of the protein-based adjuvanted Nuvaxovid (NVX-CoV2373) No-vavax vaccine for SARS-CoV-2 could increase vaccine uptake and provide immune protection from viral variants. Med Sci Monit 2022; 28: e936523. doi: 10.12659/MSM.936523.

[25] Chukwudozie OS, Duru VC, Ndiribe CC, Aborode AT, Oyebanji VO, Emikpe BO. The relevance of bioinformatics applications in the discovery of vaccine candidates and potential drugs for COVID-19 treatment. Bioinform Biol Insights 2021; 15: 11779322211002168. doi: 10.1177/11779322211002168.

[26] Bouazzaoui A, Abdellatif AAH, Al-Allaf FA, Bogari NM, Al-Dehlawi S, Qari SH. Strategies for vaccination: Conventional vaccine approaches versus new-generation strategies in combination with adjuvants. Pharmaceutics 2021; 13(2): 140. doi: 10.3390/pharmaceutics13020140.

[27] Cannataro M, Harrison A. Bioinformatics helping to mitigate the impact of COVID-19-Editorial. Brief Bioinform 2021; 22(2): 613-615.

[28] Alrabadi N, Bany-Melhem S, Alzoubi KH, Alzoubi OO, Masadeh M, Abuhammad S, et al. COVID-19 vaccination hesitancy: A review of the literature and recommendations. Curr Rev Clin Exp Pharmacol 2024; 19(1): 26-41. https://doi.org/10.2174/2772432817666220512112913.

[29] Huang T, Zhao K, Song X, Song T, Wang X, Zhang X, et al. Heterologous prime-boost immunization with DNA vaccine and modified recombinant proteins enhances immune response against Trueperella pyogenes in mice. Vaccines (Basel) 2022; 10(6): 839. doi: 10.3390/vaccines10060839.

[30] Vuitika L, Prates-Syed WA, Silva JDQ, Crema KP, Côrtes N, Lira A, et al. Vaccines against emerging and neglected infectious diseases: An overview. Vaccines 2022; 10(9): 1385. doi: 10.3390/vaccines10091385.

[31] Mbacham WF, Ayong L, Guewo-Fokeng M, Makoge V. Current situation of malaria in Africa. In: Ariey F, Gay F, Ménard R. (eds.) Malaria control and elimination. Springer: New York; 2019, p. 29-44.

[32] Wen S, Harvard KE, Gueye CS, Canavati SE, Chancellor A, Ahmed BN, et al. Targeting populations at higher risk for malaria: A survey of national malaria elimination programmes in the Asia Pacific. Malar J 2016; 15(1): 271. https://doi.org/10.1186/s12936-016-1319-1.

[33] da Silveira Mariano RM, Gonçalves AAM, de Oliveira DS, Ribeiro HS, Pereira DFS, Santos IS, et al. A review of major patents on potential malaria vaccine targets. Pathogens 2023; 12(2): 247. doi: 10.3390/ pathogens12020247.

[34] Kanoi BN, Maina M, Likhovole C, Kobia FM, Gitaka J. Malaria vaccine approaches leveraging technologies optimized in the COVID-19 era. Front Trop Dis 2022; 3: 988665. doi: 10.3389/fitd.2022.988665.

[35] Nadeem AY, Shehzad A, Islam SU, Al-Suhaimi EA, Lee YS. MosquirixTM RTS, S/AS01 vaccine development, immunogenicity, and efficacy. Vaccines (Basel) 2022; 10(5): 713. https://doi.org/10.3390/vaccines10050713.

[36] Zheng J, Pan H, Gu Y, Zuo X, Ran N, Yuan Y, et al. Prospects for malaria vaccines: Pre-erythrocytic stages, blood stages, and transmission-blocking stages. Biomed Res Int 2019; 2019: 9751471. doi: 10.1155/2019/9751471.

[37] Marques-da-Silva C, Peissig K, Kurup SP. Pre-erythrocytic vaccines against malaria. Vaccines 2020; 8(3): 400. doi: 10.1586/erv.12.92.

[38] RTS , S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 2015; 386(9988): 31-45.

[39] Guerra Mendoza Y, Garric E, Leach A, Lievens M, Ofori-Anyinam O, Pirçon JY, et al. Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: Additional data from a phase III randomized controlled trial in sub-Saharan Africa. Hum Vaccin Immunother 2019; 15(10): 2386-2398.

[40] Skwarczynski M, Chandrudu S, Rigau-Planella B, Islam MT, Cheong YS, Liu G, et al. Progress in the development of subunit vaccines against malaria. Vaccines (Basel) 2020; 8(3): 373. doi: 10.3390/vaccines8030373.

[41] Moorthy V, Binka F. R21/Matrix-M: A second malaria vaccine? Lancet 2021; 397(10287): 1782-1783.

[42] Rashidzadeh H, Tabatabaei Rezaei SJ, Adyani SM, Abazari M, Rahamooz Haghighi S, Abdollahi H, et al. Recent advances in targeting malaria with nanotechnology-based drug carriers. Pharm Dev Technol 2021; 26(8): 807-823.

[43] Pance A. Diversify and conquer: The vaccine escapism of Plasmodium falciparum. Microorganisms 2020; 8(11): 1748. doi: 10.3390/ microorganisms8111748.

[44] Datoo MS, Natama HM, Somé A, Bellamy D, Traoré O, Rouamba T, et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: A phase 1/2b randomised controlled trial. Lancet Infect Dis 2022; 22(12): 1728-1736.

[45] Nitika N, Nema S, Bharti PK. R21 vaccine: A ray of hope for malaria elimination. Asian Pac J Trop Med 2023; 16(6): 243. doi: 10.4103/1995-7645.378560.

[46] Vijayan A, Chitnis CE. Development of blood stage malaria vaccines. In: Ariey F, Gay F, Ménard R. (eds.) Malaria control and elimination. New York: Springer; 2019, p. 199-218.

[47] Molehin AJ, McManus DP, You H. Vaccines for human schistosomiasis: Recent progress, new developments and future prospects. Int J Mol Sci 2022; 23(4): 2255. doi: 10.3390/ijms23042255.

[48] Nema S, Nitika N. Monoclonal antibody: Future of malaria control and prevention. Trans R Soc Trop Med Hyg 2023; 117(9): 673-674.

[49] Salamanca DR, Gómez M, Camargo A, Cuy-Chaparro L, Molina-Franky J, Reyes C, et al. Plasmodium falciparum blood stage antimalarial vaccines: An analysis of ongoing clinical trials and new perspectives related to synthetic vaccines. Front Microbiol 2019; 10: 2712. https://www.frontiersin.org/articles/10.3389/fmicb.2019.02712.

[50] Bonam SR, Rénia L, Tadepalli G, Bayry J, Kumar HMS. Plasmodium falciparum malaria vaccines and vaccine adjuvants. Vaccines (Basel) 2021; 9(10): 1072.

[51] Parums DV. Editorial: Current status of two adjuvanted malaria vaccines and the World Health Organization (WHO) strategy to eradicate malaria by 2030. Med Sci Moni 2023; 29: e939357. doi: 10.12659/MSM.939357.

[52] Obaldia N, Stockelman MG, Otero W, Cockrill JA, Ganeshan H, Abot EN, et al. A Plasmodium vivax plasmid DNA- and adenovirus-vectored malaria vaccine encoding blood-stage antigens AMA1 and MSP142 in a prime/boost heterologous immunization regimen partially protects aotus monkeys against blood-stage challenge. Clin Vaccine Immunol 2017; 24(4): e00539-16. https://doi.org/10.1128/CVI.00539-16.

[53] Chichester JA, Green BJ, Jones RM, Shoji Y, Miura K, Long CA, et al. Safety and immunogenicity of a plant-produced Pfs25 virus-like particle as a transmission blocking vaccine against malaria: A phase 1 dose-escalation study in healthy adults. Vaccine 2018; 36(39): 5865-5871.

[54] Scaria PV, Chen BB, Rowe CG, Alani N, Muratova OV, Barnafo EK, et al. Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230. Vaccine 2020; 38(34): 5480-5489.

[55] Alves KCS, Guimarães JM, de Almeida MEM, Mariúba LAM. Plasmodium falciparum merozoite surface protein 3 as a vaccine candidate: A brief review. Rev Inst Med Trop Sao Paulo 2022; 64: e23. doi: 10.1590/S1678-9946202264023.

[56] Koger-Pease C, Perera DJ, Ndao M. Recent advances in the development of adenovirus-vectored vaccines for parasitic infections. Pharmaceuticals 2023; 16(3): 334. doi: 10.1590/S1678-9946202264023.

[57] Kurtovic L, Reiling L, Opi DH, Beeson JG. Recent clinical trials inform the future for malaria vaccines. Commun Med 2021; 1(1): 1-5.

[58] Frimpong A, Kusi KA, Ofori MF, Ndifon W. Novel strategies for malaria vaccine design. Front Immunol 2018; 9: 2769. https://www.frontiersin.org/articles/10.3389/fimmu.2018.02769.

[59] Duffy PE. Current approaches to malaria vaccines. Curr Opin Microbiol 2022; 70: 102227. https://doi.org/10.1016/j.mib.2022.102227.

[60] Silva NM, Santos NC, Martins IC. Dengue and Zika viruses: Epidemiological history, potential therapies, and promising vaccines. Trop Med Infect Dis 2020; 5(4): 150. doi: 10.3390/tropicalmed5040150.

[61] Tremblay N, Freppel W, Sow AA, Chatel-Chaix L. The interplay between dengue virus and the human innate immune system: A game of hide and seek. Vaccines 2019; 7(4): 145.

[62] Norshidah H, Vignesh R, Lai NS. Updates on dengue vaccine and antiviral: Where are we heading? Molecules 2021; 26(22): 6768.

[63] Zeyaullah M, Muzammil K, AlShahrani AM, Khan N, Ahmad I, Alam MS, et al. Preparedness for the dengue epidemic: Vaccine as a viable approach. Vaccines 2022; 10(11): 1940. doi: 10.3390/vaccines7040145.

[64] Tully D, Griffiths CL. Dengvaxia: The world’s first vaccine for prevention of secondary dengue. Ther Adv Vaccines Immunother 2021; 9: 25151355211015840.

[65] Wilder-Smith A. Dengue vaccine development by the year 2020: Challenges and prospects. Curr Opin Virol 2020; 43: 71-78.

[66] Durbin AP, Pierce KK, Kirkpatrick BD, Grier P, Sabundayo BP, He H, et al. Immunogenicity and safety of a tetravalent recombinant subunit dengue vaccine in adults previously vaccinated with a live attenuated tetravalent dengue vaccine: Results of a phase I randomized clinical trial. Am J Trop Med Hyg 2020; 103(2): 855-863.

[67] Manoff SB, Sausser M, Falk Russell A, Martin J, Radley D, Hyatt D, et al. Immunogenicity and safety of an investigational tetravalent recombinant subunit vaccine for dengue: Results of a phase J randomized clinical trial in flavivirus-naïve adults. Hum Vaccin Immunother 2019; 15(9): 2195-2204.

[68] Wahongan IF, Suoth EJ, Fatimawali , Alhumaid S, Albayat H, Aljeldah M, et al. Designing an epitope-based peptide vaccine derived from RNA- dependent RNA polymerase (RdRp) against dengue virus serotype 2. Vaccines 2022; 10(10): 1734. doi: 10.3390/vaccines10101734.

[69] Obi JO, Gutiérrez-Barbosa H, Chua JV, Deredge DJ. Current trends and limitations in dengue antiviral research. Trop Med Infect Dis 2021; 6(4): 180.

[70] McCann N, O’Connor D, Lambe T, Pollard AJ. Viral vector vaccines. Curr Opin Immunol 2022; 77: 102210. doi: 10.1016/j.coi.2022.102210.

[71] Masmejan S, Musso D, Vouga M, Pomar L, Dashraath P, Stojanov M, et al. Zika virus. Pathogens 2020; 9(11): 898. doi: 10.3390/ pathogens9110898.

[72] Montalvo Zurbia-Flores G, Reyes-Sandoval A, Kim YC. Chikungunya virus: Priority pathogen or passing trend? Vaccines 2023; 11(3): 568. doi: 10.3390/vaccines11030568.

[73] Pattnaik A, Sahoo BR, Pattnaik AK. Current status of Zika virus vaccines: Successes and challenges. Vaccines 2020; 8(2): 266. doi: 10.3390/vaccines8020266.

[74] Poland GA, Ovsyannikova IG, Kennedy RB. Zika vaccine development: Current status. Mayo Clin Proc 2019; 94(12): 2572-2586.

[75] Richner JM, Diamond MS. Zika virus vaccines: Immune response, current status, and future challenges. Curr Opin Immunol 2018; 53: 130-136.

[76] Araujo SC, Pereira LR, Alves RPS, Andreata-Santos R, Kanno AI, Ferreira LCS, et al. Anti-flavivirus vaccines: Review of the present situation and perspectives of subunit vaccines produced in Escherichia coli. Vaccines 2020; 8(3): 492. doi: 10.3390/vaccines8030492.

[77] Lee JK, Shin OS. Advances in Zika virus-host cell interaction: Current knowledge and future perspectives. Int J Mol Sci 2019; 20(5): 1101. doi: 10.3390/ijms20051101.

[78] Prow NA, Liu L, McCarthy MK, Walters K, Kalkeri R, Geiger J, et al. The vaccinia virus based Sementis Copenhagen Vector vaccine against Zika and chikungunya is immunogenic in non-human primates. NPJ Vaccines 2020; 5(1): 1-10.

[79] Castanha PMS, Marques ETA. A glimmer of hope: Recent updates and future challenges in Zika vaccine development. Viruses 2020; 12(12): 1371. doi: 10.3390/v12121371.

[80] Gao S, Song S, Zhang L. Recent progress in vaccine development against chikungunya virus. Front Microbiol 2019; 10: 2881. https://www.frontiersin.org/articles/10.3389/fmicb.2019.02881.

[81] Dora EG, Rossi SL, Weaver SC, Tucker SN, Mateo R. An adjuvanted adenovirus 5-based vaccine elicits neutralizing antibodies and protects mice against chikungunya virus-induced footpad swelling. Vaccine 2019; 37(24): 3146-3150.

[82] Tan Y, Pickett BE, Shrivastava S, Gresh L, Balmaseda A, Amedeo P, et al. Differing epidemiological dynamics of Chikungunya virus in the Americas during the 2014-2015 epidemic. PLoS Negl Trop Dis 2018; 12(7): e0006670. doi: 10.1371/journal.pntd.0006670.

[83] Tang N, Zhang Y, Shen Z, Yao Y, Nair V. Application of CRISPR-Cas9 editing for virus engineering and the development of recombinant viral vaccines. CRISPR J 2021; 4(4): 477-490.

[84] Naeem M, Alkhodairy HF, Ashraf I, Khalil AB. CRISPR/Cas system toward the development of next-generation recombinant vaccines: Current scenario and future prospects. Arab J Sci Eng 2023; 48(1): 1-11.

[85] Teng M, Yao Y, Nair V, Luo J. Latest advances of virology research using CRISPR/Cas9-based gene-editing technology and its application to vaccine development. Viruses 2021; 13(5): 779. doi: 10.3390/v13050779.

[86] Najafi S, Tan SC, Aghamiri S, Raee P, Ebrahimi Z, Jahromi ZK, et al. Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections. Biomed Pharmacother 2022; 148: 112743. doi: 10.1016/j.biopha.2022.112743.

[87] Mehta A, Merkel OM. Immunogenicity of Cas9 protein. J Pharm Sci 2020; 109(1): 62-67.

[88] Chen F, Alphonse M, Liu Q. Strategies for nonviral nanoparticle-based delivery of CRISPR/Cas9 therapeutics. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020; 12(3): e1609. doi: 10.1002/wnan.1609.

[89] Tiwari PK, Ko TH, Dubey R, Chouhan M, Tsai LW, Singh HN, et al. CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: From bench to clinics. Front Mol Biosci 2023; 10: 1214489. https://www.frontiersin.org/articles/10.3389/fmolb.2023.1214489.

[90] Mazloum A, Karagyaur M, Chernyshev R, van Schalkwyk A, Jun M, Qiang F, et al. Post-genomic era in agriculture and veterinary science: Successful and proposed application of genetic targeting technologies. Front Vet Sci 2023; 10: 1180621. doi: 10.3389/fvets.2023.1180621.

[91] Karn V, Sandhya S, Hsu W, Parashar D, Singh HN, Jha NK, et al. CRISPR/Cas9 system in breast cancer therapy: Advancement, limitations and future scope. Cancer Cell Int 2022; 22(1): 234. doi: 10.1186/s12935-022-02654-3.

[92] Zhang X, Zhang C, Liang C, Li B, Meng F, Ai Y. CRISPR-Cas9 based bacteriophage genome editing. Microbiol Spectr 2022; 10(4): e00820-22. doi: 10.1128/spectrum.00820-22.

[93] Leleux J, Roy K. Micro and nanoparticle-based delivery systems for vaccine immunotherapy: An immunological and materials perspective. Adv Healthc Mater 2013; 2(1): 72-94.

[94] Perotti M, Perez L. Virus-like particles and nanoparticles for vaccine development against HCMV. Viruses 2020; 12(1): 35. doi: 10.3390/v12010035.

[95] Huang J. Virus-like particles in vaccine development for infectious diseases. Highl Sci Eng Technol 2023; 36: 1525-1531.

[96] Tornesello AL, Tagliamonte M, Buonaguro FM, Tornesello ML, Buonaguro L. Virus-like particles as preventive and therapeutic cancer vaccines. Vaccines 2022; 10(2): 227. doi: 10.3390/vaccines10020227.

[97] Garg H, Mehmetoglu-Gurbuz T, Joshi A. Virus like particles (VLP) as multivalent vaccine candidate against Chikungunya, Japanese encephalitis, Yellow Fever and Zika virus. Sci Rep 2020; 10(1): 4017. https://doi.org/10.1038/s41598-020-61103-1.

[98] Veena Rani N, Kapoor N, Krishnan A. Efficient generation and characterization of chimeric dengue viral-like particles. Biochem Biophys Res Commun 2023; 654: 10-17. https://doi.org/10.1016/j.bbrc.2023.02.052.

[99] Cuevas-Juárez E, Pando-Robles V, Palomares LA. Flavivirus vaccines: Virus-like particles and single-round infectious particles as promising alternatives. Vaccine 2021; 39(48): 6990-7000.

[100] Gomes AC, Mohsen M, Bachmann MF. Harnessing nanoparticles for immunomodulation and vaccines. Vaccines 2017; 5(1): 6. doi: 10.3390/ vaccines5010006.

[101] Ikwuagwu B, Tullman-Ercek D. Virus-like particles for drug delivery: A review of methods and applications. Curr Opin Biotechnol 2022; 78: 102785. doi: 10.1016/j.copbio.2022.102785.

[102] Naupu PN, van Zyl AR, Rybicki EP, Hitzeroth II. Immunogenicity of plant-produced human papilloma-virus (HPV) virus-like particles (VLPs). Vaccines 2020; 8(4): 740. doi: 10.3390/vaccines8040740.

[103] Pushko P, Tretyakova I. Influenza virus like particles (VLPs): Opportunities for H7N9 vaccine development. Viruses 2020; 12(5): 518. doi: 10.3390/v12050518.

[104] de Pinho Favaro MT, Atienza-Garriga J, Martínez-Torró C, Parladé E, Vázquez E, Corchero JL, et al. Recombinant vaccines in 2022: A perspective from the cell factory. Microbial Cell Factories 2022; 21(1): 203. doi: 10.1186/s12934-022-01929-8.

[105] Sung HD, Kim N, Lee Y, Lee EJ. Protein-based nanoparticle vaccines for SARS-CoV-2. In J Mol Sci 2021; 22(24): 13445.

[106] García-Montero C, Fraile-Martínez O, Bravo C, Torres-Carranza D, Sanchez-Trujillo L, Gómez-Lahoz AM, et al. An updated review of SARS-CoV-2 vaccines and theimportance of effective vaccination programs in pandemic times. Vaccines 2021; 9(5): 433. doi: 10.3390/ vaccines9050433.

[107] Aziz S, Waqas M, Halim SA, Ali A, Iqbal A, Iqbal M, et al. Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in silico approach. Front Immunol 2022; 13: 956776. https://www.frontiersin.org/articles/10.3389/fimmu.2022.956776.

[108] Oyarzun P, Kashyap M, Fica V, Salas-Burgos A, Gonzalez-Galarza FF, McCabe A, et al. A proteome-wide immunoinformatics tool to accelerate T-cell epitope discovery and vaccine design in the context of emerging infectious diseases: An ethnicity-oriented approach. Front Immunol 2021; 12: 598778. https://www.frontiersin.org/articles/10.3389/fimmu.2021.598778.

[109] Soleymani S, Tavassoli A, Housaindokht MR. An overview of progress from empirical to rational design in modern vaccine development, with an emphasis on computational tools and immunoinformatics approaches. Comput Biol Med 2022; 140: 105057. doi: 10.1016/ j.compbiomed.2021.105057.

[110] Gul S, Ahmad S, Ullah A, Ismail S, Khurram M, Tahir Ul Qamar M, et al. Designing a recombinant vaccine against Provideneia rettgeri using immunoinformatics approach. Vaccines 2022; 10(2): 189. doi: 10.3390/vaccines10020189.

[111] Tang Y, Fan W, Chen G, Zhang M, Tang X, Wang H, et al. Recombinant cancer nanovaccine for targeting tumor-associated macrophage and remodeling tumor microenvironment. Nano Today 2021; 40: 101244. https://doi.org/10.1016/j.nantod.2021.101244.

[112] Buonaguro L, Tagliamonte M. Selecting target antigens for cancer vaccine development. Vaccines 2020; 8(4): 615. https://doi.org/10.3390/vaccines8040615.

[113] Kerr MD, McBride DA, Chumber AK, Shah NJ. Combining therapeutic vaccines with chemo- and immunotherapies in the treatment of cancer. Expert Opin Drug Discov 2020; 16(1): 89-99. https://doi.org/10.1080/17460441.2020.1811673.

[114] Sutherland SIM, Ju X, Horvath LG, Clark GJ. Moving on from sipuleucel-T: New dendritic cell vaccine strategies for prostate cancer. Front Immunol 2021; 12: 641307. https://doi.org/10.3389/fimmu.2021.641307.

[115] Laher F, Bekker LG, Garrett N, Lazarus EM, Gray GE. Review of preventative HIV vaccine clinical trials in South Africa. Arch Virol 2020; 165(11): 2439-2452. https://doi.org/10.1007/s00705-020-04777-2.

[116] Filin IY, Kitaeva KV, Rutland CS, Rizvanov AA, Solovyeva VV. Recent advances in experimental dendritic cell vaccines for cancer. Front Oncol 2021; 11: 730824. https://doi.org/10.3389/fonc.2021.730824.

[117] Mangion M, Gélinas JF, Bakhshi Zadeh Gashti A, Azizi H, Kiesslich S, Nassoury N, et al. Evaluation of novel HIV vaccine candidates using recombinant vesicular stomatitis virus vector produced in serum-free vero cell cultures. Vaccine 2020; 38(50): 7949-7955. https://doi.org/10.1016/j.vaccine.2020.10.058.

[118] Hokello J, Sharma AL, Tyagi M. An update on the HIV DNA vaccine strategy. Vaccines 2020; 9(6): 605. https://doi.org/10.3390/vaccines9060605.

[119] Kim J, Vasan S, Kim JH, Ake JA. Current approaches to HIV vaccine development: A narrative review. J Int AIDS Soc 2021; 24(Suppl 7): e25793. https://doi.org/10.1002/jia2.25793.

[120] Sultana M, Hasan N, Mahib MR, Islam MM. Systematic mutational analysis of epitope-grafted ED3 immunogenicity reveals a DENV3-DENV4 bi-serospecific ED3 mutant. Asian Pac J Trop Med 2022; 15(2): 63-70.

[121] Zakaria NM, Abbas MA, Suppian R. CRX-527 as a candidate adjuvant in a recombinant BCG-based malaria vaccine. Asian Pac J Trop Biomed 2024; 14(1): 1-7.

[122] Mukherjee S, Tworowski D, Detroja R, Mukherjee SB, Frenkel-Morgenstern M. Immunoinformatics and structural analysis for identification of immunodominant epitopes in SARS-CoV-2 as potential vaccine targets. Vaccines 2020; 8(2): 290.

[123] Bhardwaj A, Sharma R, Grover A. Immuno-informatics guided designing of a multi-epitope vaccine against dengue and Zika. J Biomol Struct Dyn 2023; 41(1): 1-15.