Exploration of Immunology

Table 2. Differences between subunit, protein-based, reverse vaccinology, and messenger RNA (m-RNA)-based vaccines

Vaccine type	Mechanism	Advantages	Limitations	Examples	Reference
Subunit vaccines	Use isolated components (e.g., proteins, polysaccharides)	Safe; no live pathogens	Lower immunogenicity; often requires adjuvants; challenging to produce epitopes for all strains	Hepatitis B [recombinant hepatitis B surface antigen (HBsAg)], human papillomavirus (HPV) (Gardasil^®)	[44]
Protein-based vaccines	Utilize pathogen-specific proteins (often purified or recombinant)	Highly specific; can be combined with adjuvants; stable	Limited efficacy against pathogens with rapid mutation	Novavax COVID-19 vaccine (protein subunit)	[45]
Reverse vaccinology	Uses genomic sequencing to identify antigenic targets	Enables vaccine development for difficult pathogens; faster discovery	Computational predictions may not always yield effective antigens	Multi-epitope-based peptide vaccine against avian rotavirus (AvRV) strains	[47]
m-RNA vaccines	Deliver m-RNA encoding viral or pathogen-derived proteins	Rapid development; no need for live pathogens; strong cellular/humoral immunity	Requires cold chain storage; risk of instability	Pfizer-BioNTech and Moderna COVID-19 vaccines	[46]

Return to article view

Declarations

Author contributions

AK and FA: Conceptualization, Data curation, Formal analysis, Writing—original draft, Writing—review & editing. BKS: Formal analysis. AAAA, YM, and VM: Validation, Visualization, Methodology, Formal analysis, Supervision, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

All datasets analyzed for this study are included in the manuscript.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Murphy FA. EPIDEMIOLOGY OF VIRAL DISEASES. In: Granoff A, Webster RG, editors. Encyclopedia of Virology (Second Edition). Oxford: Elsevier; 1999. pp. 482–7. [DOI] [PMC]

Yousefi Z, Aria H, Ghaedrahmati F, Bakhtiari T, Azizi M, Bastan R, et al. An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy. Front Immunol. 2022;12:805695. [DOI] [PubMed] [PMC]

Vector-borne diseases [Internet]. WHO; c2025 [cited 2025 Feb 26]. Available from: https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases

Li XC, Zhang YY, Zhang QY, Liu JS, Ran JJ, Han LF, et al. Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021. Infect Dis Poverty. 2024;13:71. [DOI] [PubMed] [PMC]

Coccia M. Pandemic Prevention: Lessons from COVID-19. Encyclopedia. 2021;1:433–44. [DOI]

Jensen A, Stromme M, Moyassari S, Chadha AS, Tartaglia MC, Szoeke C, et al. COVID-19 vaccines: Considering sex differences in efficacy and safety. Contemp Clin Trials. 2022;115:106700. [DOI] [PubMed] [PMC]

Daitch V, Turjeman A, Poran I, Tau N, Ayalon-Dangur I, Nashashibi J, et al. Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis. Trials. 2022;23:1038. [DOI] [PubMed] [PMC]

Plotkin SA, Orenstein WA, Offit PA, Edwards KM, editors. Plotkin’s Vaccines. 7th ed. Elsevier; 2018. [DOI]

Al Fayez N, Nassar MS, Alshehri AA, Alnefaie MK, Almughem FA, Alshehri BY, et al. Recent Advancement in mRNA Vaccine Development and Applications. Pharmaceutics. 2023;15:1972. [DOI] [PubMed] [PMC]

10.

Ali H, Akbar M, Iqbal B, Ali F, Sharma NK, Kumar N, et al. Virosome: An engineered virus for vaccine delivery. Saudi Pharm J. 2023;31:752–64. [DOI] [PubMed] [PMC]

11.

Stewart AJ, Devlin PM. The history of the smallpox vaccine. J Infect. 2006;52:329–34. [DOI] [PubMed]

12.

Psarris A, Sindos M, Daskalakis G, Chondrogianni ME, Panayiotou S, Antsaklis P, et al. Immunizations during pregnancy: How, when and why. Eur J Obstet Gynecol Reprod Biol. 2019;240:29–35. [DOI] [PubMed]

13.

Orsini D, Valchi L, Minet C, Martini M. The history of polio vaccination with “Sabin’s OPV” 60 years after its introduction in Italy: an unforgivable “delay”. J Prev Med Hyg. 2024;65:E105–12. [DOI] [PubMed] [PMC]

14.

Hendriks J, Blume S. Measles vaccination before the measles-mumps-rubella vaccine. Am J Public Health. 2013;103:1393–401. [DOI] [PubMed] [PMC]

15.

Zhao H, Zhou X, Zhou YH. Hepatitis B vaccine development and implementation. Hum Vaccin Immunother. 2020;16:1533–44. [DOI] [PubMed] [PMC]

16.

Trombetta CM, Kistner O, Montomoli E, Viviani S, Marchi S. Influenza Viruses and Vaccines: The Role of Vaccine Effectiveness Studies for Evaluation of the Benefits of Influenza Vaccines. Vaccines (Basel). 2022;10:714. [DOI] [PubMed] [PMC]

17.

Aggarwal S, Agarwal P, Singh AK. Human papilloma virus vaccines: A comprehensive narrative review. Cancer Treat Res Commun. 2023;37:100780. [DOI] [PubMed]

18.

Coulborn RM, Bastard M, Peyraud N, Gignoux E, Luquero F, Guai B, et al. Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo. Lancet Infect Dis. 2024;24:602–10. [DOI] [PubMed]

19.

Demongeot J, Fougère C. mRNA COVID-19 Vaccines—Facts and Hypotheses on Fragmentation and Encapsulation. Vaccines (Basel). 2023;11:40. [DOI] [PubMed] [PMC]

20.

Mendonça SA, Lorincz R, Boucher P, Curiel DT. Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic. NPJ Vaccines. 2021;6:97. [DOI] [PubMed] [PMC]

21.

Kayesh MEH, Nazneen H, Kohara M, Tsukiyama-Kohara K. An effective pan-serotype dengue vaccine and enhanced control strategies could help in reducing the severe dengue burden in Bangladesh–A perspective. Front Microbiol. 2024;15:1423044. [DOI] [PubMed] [PMC]

22.

Dhalaria P, Kapur S, Singh AK, Verma A, Priyadarshini P, Taneja G. Potential impact of rotavirus vaccination on reduction of childhood diarrheal disease in India: An analysis of National Family Health Survey-5. Vaccine X. 2023;14:100319. [DOI] [PubMed] [PMC]

23.

Kessels J, Tarantola A, Salahuddin N, Blumberg L, Knopf L. Rabies post-exposure prophylaxis: A systematic review on abridged vaccination schedules and the effect of changing administration routes during a single course. Vaccine. 2019;37:A107–17. [DOI] [PubMed]

24.

Ghattas M, Dwivedi G, Lavertu M, Alameh MG. Vaccine Technologies and Platforms for Infectious Diseases: Current Progress, Challenges, and Opportunities. Vaccines (Basel). 2021;9:1490. [DOI] [PubMed] [PMC]

25.

Galagali PM, Kinikar AA, Kumar VS. Vaccine Hesitancy: Obstacles and Challenges. Curr Pediatr Rep. 2022;10:241–8. [DOI] [PubMed] [PMC]

26.

Plotkin S. History of vaccination. Proc Natl Acad Sci U S A. 2014;111:12283–7. [DOI] [PubMed] [PMC]

27.

Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005;18:21–5. [DOI] [PubMed] [PMC]

28.

A brief history of vaccines [Internet]. WHO; c2025 [cited 2025 Feb 26]. Available from: https://www.who.int/news-room/spotlight/history-of-vaccination/a-brief-history-of-vaccination

29.

Baicus A. History of polio vaccination. World J Virol. 2012;1:108–14. [DOI] [PubMed] [PMC]

30.

Measles Vaccination [Internet]. [cited 2025 Feb 26]. Available from: https://www.cdc.gov/vaccines/vpd/mmr/public/index.html

31.

Nascimento IP, Leite LCC. Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res. 2012;45:1102–11. [DOI] [PubMed] [PMC]

32.

Wang YS, Kumari M, Chen GH, Hong MH, Yuan JP, Tsai JL, et al. mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications. J Biomed Sci. 2023;30:84. [DOI] [PubMed] [PMC]

33.

Versteeg L, Pollet J. mRNA Vaccines for Malaria and Other Parasitic Pathogens. In: Szabo GT, Pardi N, editors. Trends in mRNA Vaccine Research. Wiley‐VCH GmbH; 2025. pp. 303–23. [DOI]

34.

Deng S, Liang H, Chen P, Li Y, Li Z, Fan S, et al. Viral Vector Vaccine Development and Application during the COVID-19 Pandemic. Microorganisms. 2022;10:1450. [DOI] [PubMed] [PMC]

35.

Aqib AI, Anjum AA, Islam MA, Murtaza A, Rehman AU. Recent Global Trends in Vaccinology, Advances and Challenges. Vaccines (Basel). 2023;11:520. [DOI] [PubMed] [PMC]

36.

Draper SJ, Heeney JL. Viruses as vaccine vectors for infectious diseases and cancer. Nat Rev Microbiol. 2010;8:62–73. [DOI] [PubMed]

37.

Brisse M, Vrba SM, Kirk N, Liang Y, Ly H. Emerging Concepts and Technologies in Vaccine Development. Front Immunol. 2020;11:583077. [DOI] [PubMed] [PMC]

38.

Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021;21:83–100. [DOI] [PubMed] [PMC]

39.

Pambudi NA, Sarifudin A, Gandidi IM, Romadhon R. Vaccine cold chain management and cold storage technology to address the challenges of vaccination programs. Energy Rep. 2022;8:955–72. [DOI]

40.

Bayani F, Hashkavaei NS, Arjmand S, Rezaei S, Uskoković V, Alijanianzadeh M, et al. An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines. Prog Biophys Mol Biol. 2023;178:32–49. [DOI] [PubMed] [PMC]

41.

Coccia M. Sources of technological innovation: Radical and incremental innovation problem-driven to support competitive advantage of firms. Technol Anal Strategic Manage. 2017;29:1048–61. [DOI]

42.

Coccia M. Problem-driven innovations in drug discovery: Co-evolution of the patterns of radical innovation with the evolution of problems. Health Policy Technol. 2016;5:143–55. [DOI]

43.

Tombacz I. Design and Development of mRNA Vaccines to Combat the COVID -19 Pandemic. In: Szabo GT, Pardi N, editors. Trends in mRNA Vaccine Research. Wiley‐VCH GmbH; 2025. pp. 241–58. [DOI]

44.

Wei Q, Liu S, Huang X, Xin H, Ding J. Immunologically effective biomaterials-enhanced vaccines against infection of pathogenic microorganisms. Biosaf Health. 2023;5:45–61. [DOI] [PubMed] [PMC]

45.

Chiba S, Halfmann PJ, Iida S, Hirata Y, Sato Y, Kuroda M, et al. Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2. Vaccine. 2023;41:6025–35. [DOI] [PubMed]

46.

Gote V, Bolla PK, Kommineni N, Butreddy A, Nukala PK, Palakurthi SS, et al. A Comprehensive Review of mRNA Vaccines. Int J Mol Sci. 2023;24:2700. [DOI] [PubMed] [PMC]

47.

Hasan M, Ahmed S, Imranuzzaman M, Bari R, Roy S, Hasan MM, et al. Designing and development of efficient multi-epitope-based peptide vaccine candidate against emerging avian rotavirus strains: A vaccinomic approach. J Genet Eng Biotechnol. 2024;22:100398. [DOI] [PubMed] [PMC]

48.

Zhang X, Sun Y, Zhang J, Zhang J, Wang J, Hu C, et al. Construction and evaluation of glycoprotein-based nucleic acid vaccines for Marburg virus. Med Microbiol Immunol. 2024;214:1. [DOI] [PubMed]

49.

Gopinathan U, Peacocke E, Gouglas D, Ottersen T, Røttingen JA. R&D for Emerging Infectious Diseases of Epidemic Potential: Sharing Risks and Benefits Through a New Coalition. In: Eccleston-Turner M, Brassington I, editors. Infectious Diseases in the New Millennium: Legal and Ethical Challenges. Cham: Springer International Publishing; 2020. pp. 137–65. [DOI]

50.

Excler JL, Saville M, Berkley S, Kim JH. Vaccine development for emerging infectious diseases. Nat Med. 2021;27:591–600. [DOI] [PubMed]

51.

Bill RM. Recombinant protein subunit vaccine synthesis in microbes: a role for yeast? J Pharm Pharmacol. 2015;67:319–28. [DOI] [PubMed]

52.

Heidary M, Kaviar VH, Shirani M, Ghanavati R, Motahar M, Sholeh M, et al. A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19. Front Microbiol. 2022;13:927306. [DOI] [PubMed] [PMC]

53.

Ho JK, Jeevan-Raj B, Netter HJ. Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms. Viruses. 2020;12:126. [DOI] [PubMed] [PMC]

54.

Sarkar B, Ullah MA, Araf Y. A systematic and reverse vaccinology approach to design novel subunit vaccines against Dengue virus type-1 (DENV-1) and human Papillomavirus-16 (HPV-16). Inf Med Unlocked. 2020;19:100343. [DOI]

55.

Ganesh Kumar S, Krupakar P, Sakthivel J, Chirayu P. Designing of a novel and potent HPV66 L1 major capsid protein-epitope based therapeutic vaccine against Human Papillomavirus (HPV): A bioinformatics approach. J Environ Biol. 2024;45:130–8. [DOI]

56.

Vaccine Types [Internet]. Courtesy: National Institute of Allergy and Infectious Diseases; [cited 2025 Feb 26]. Available from: https://www.niaid.nih.gov/research/vaccine-types

57.

Rohokale R, Guo Z. Development in the Concept of Bacterial Polysaccharide Repeating Unit-Based Antibacterial Conjugate Vaccines. ACS Infect Dis. 2023;9:178–212. [DOI] [PubMed] [PMC]

58.

Bagnoli F, Baudner B, Mishra RPN, Bartolini E, Fiaschi L, Mariotti P, et al. Designing the next generation of vaccines for global public health. OMICS. 2011;15:545–66. [DOI] [PubMed]

59.

Rappuoli R. Reverse vaccinology. Curr Opin Microbiol. 2000;3:445–50. [DOI] [PubMed]

60.

Huffman A, Ong E, Hur J, D’Mello A, Tettelin H, He Y. COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning. Brief Bioinform. 2022;23:bbac190. [DOI] [PubMed] [PMC]

61.

Kanampalliwar AM. Reverse Vaccinology and Its Applications. Methods Mol Biol. 2020;2131:1–16. [DOI] [PubMed]

62.

Islam SI, Mou MJ, Sanjida S. Application of reverse vaccinology for designing of an mRNA vaccine against re-emerging marine birnavirus affecting fish species. Inf Med Unlocked. 2022;30:100948. [DOI]

63.

Ibrahim HS, Kafi SK. A Computational Vaccine Designing Approach for MERS-CoV Infections. Methods Mol Biol. 2020;2131:39–145. [DOI] [PubMed] [PMC]

64.

Aslam S, Ashfaq UA, Zia T, Aslam N, Alrumaihi F, Shahid F, et al. Proteome based mapping and reverse vaccinology techniques to contrive multi-epitope based subunit vaccine (MEBSV) against Streptococcus pyogenes. Infect Genet Evol. 2022;100:105259. [DOI] [PubMed]

65.

Haq AU, Khan A, Khan J, Irum S, Waheed Y, Ahmad S, et al. Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach. Vaccines (Basel). 2021;9:1327. [DOI] [PubMed] [PMC]

66.

Snehlata, Teja KB, Mukherjee B. Chapter 1 - Application of CRISPR-Based Diagnostic Tools in Detecting SARS-CoV-2 Infection. In: Chatterjee S, editor. COVID-19: Tackling Global Pandemics through Scientific and Social Tools. Academic Press; 2022. pp. 1–13. [DOI]

67.

Liebal UW, Phan ANT, Sudhakar M, Raman K, Blank LM. Machine Learning Applications for Mass Spectrometry-Based Metabolomics. Metabolites. 2020;10:243. [DOI] [PubMed] [PMC]

68.

Magazzino C, Mele M, Coccia M. A machine learning algorithm to analyse the effects of vaccination on COVID-19 mortality. Epidemiol Infect. 2022;150:e168. [DOI] [PubMed] [PMC]

69.

Bharadhwaj VS, Ali M, Birkenbihl C, Mubeen S, Lehmann J, Hofmann-Apitius M, et al. CLEP: a hybrid data- and knowledge-driven framework for generating patient representations. Bioinformatics. 2021;37:3311–8. [DOI] [PubMed] [PMC]

70.

Szabo GT, Pardi N, editors. Trends in mRNA Vaccine Research. Wiley‐VCH GmbH; 2025. [DOI]

71.

Fatima M, Park PG, Hong KJ. Clinical advancements in mRNA vaccines against viral infections. Clin Immunol. 2025;271:110424. [DOI] [PubMed]

72.

See SA, Bhassu S, Tang SS, Yusoff K. Newly developed mRNA vaccines induce immune responses in Litopenaeus vannamei shrimps during primary vaccination. Dev Comp Immunol. 2025;162:105264. [DOI] [PubMed]

73.

Pardi N, Hogan MJ, Weissman D. Recent advances in mRNA vaccine technology. Curr Opin Immunol. 2020;65:14–20. [DOI] [PubMed]

74.

Kowalzik F, Schreiner D, Jensen C, Teschner D, Gehring S, Zepp F. mRNA-Based Vaccines. Vaccines (Basel). 2021;9:390. [DOI] [PubMed] [PMC]

75.

Verbeke R, Cheng MHY, Cullis PR. A Historical Overview on mRNA Vaccine Development. In: Szabo GT, Pardi N, editors. Trends in mRNA Vaccine Research. Wiley‐VCH GmbH; 2025. pp. 1–27. [DOI]

76.

Devarkar SC, Wang C, Miller MT, Ramanathan A, Jiang F, Khan AG, et al. Structural basis for m7G recognition and 2'-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I. Proc Natl Acad Sci U S A. 2016;113:596–601. [DOI] [PubMed] [PMC]

77.

Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines. 2020;5:11. [DOI] [PubMed] [PMC]

78.

Barrett SP, Salzman J. Circular RNAs: analysis, expression and potential functions. Development. 2016;143:1838–47. [DOI] [PubMed] [PMC]

79.

Jin L, Zhou Y, Zhang S, Chen SJ. mRNA vaccine sequence and structure design and optimization: Advances and challenges. J Biol Chem. 2025;301:108015. [DOI] [PubMed] [PMC]

80.

Verbeke R, Hogan MJ, Loré K, Pardi N. Innate immune mechanisms of mRNA vaccines. Immunity. 2022;55:1993–2005. [DOI] [PubMed] [PMC]

81.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. 4th ed. New York: Garland Science; 2002.

82.

Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125:S3–23. [DOI] [PubMed] [PMC]

83.

Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011;3:920–40. [DOI] [PubMed] [PMC]

84.

Cui L, Ma R, Cai J, Guo C, Chen Z, Yao L, et al. RNA modifications: importance in immune cell biology and related diseases. Signal Transduct Target Ther. 2022;7:334. [DOI] [PubMed] [PMC]

85.

Conry RM, LoBuglio AF, Wright M, Sumerel L, Pike MJ, Johanning F, et al. Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res. 1995;55:1397–400. [PubMed]

86.

Chehelgerdi M, Chehelgerdi M. The use of RNA-based treatments in the field of cancer immunotherapy. Mol Cancer. 2023;22:106. [DOI] [PubMed] [PMC]

87.

Fiedler K, Lazzaro S, Lutz J, Rauch S, Heidenreich R. mRNA Cancer Vaccines. In: Walther W, editor. Current Strategies in Cancer Gene Therapy. Cham: Springer International Publishing; 2016. pp. 61–85. [DOI] [PubMed]

88.

Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017;547:222–6. [DOI] [PubMed]

89.

Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al.; mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med. 2020;383:1920–31. [DOI] [PubMed] [PMC]

90.

Carabelli AM, Peacock TP, Thorne LG, Harvey WT, Hughes J; COVID-19 Genomics UK Consortium; Peacock SJ, Barclay WS, de Silva TI, Towers GJ, Robertson DL. SARS-CoV-2 variant biology: immune escape, transmission and fitness. Nat Rev Microbiol. 2023;21:162–77. [DOI] [PubMed] [PMC]

91.

Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020;383:2439–50. [DOI] [PubMed] [PMC]

92.

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al.; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383:2603–15. [DOI] [PubMed] [PMC]

93.

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al.; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384:403–16. [DOI] [PubMed] [PMC]

94.

Zuiani A, Dulberger CL, De Silva NS, Marquette M, Lu YJ, Palowitch GM, et al. A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease. Cell. 2024;187:1363–73.e12. [DOI] [PubMed]

95.

A Study to Investigate The Safety, Tolerability, And Immune Response of a Range of Doses of mRNA-1769 Compared With Placebo in Healthy Participants From ≥18 Years of Age to <50 Years of Age [Internet]. [cited 2025 Feb 26]. Available from: https://clinicaltrials.gov/study/NCT05995275?cond=NCT05995275&term=Vaccine&rank=1

96.

A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines [Internet]. [cited 2025 Feb 26]. Available from: https://clinicaltrials.gov/study/NCT05988203?cond=NCT05988203&term=Vaccine&rank=1

97.

Mucker EM, Freyn AW, Bixler SL, Cizmeci D, Atyeo C, Earl PL, et al. Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates. Cell. 2024;187:5540–53.e10. [DOI] [PubMed]

98.

Krammer F. The human antibody response to influenza A virus infection and vaccination. Nat Rev Immunol. 2019;19:383–97. [DOI] [PubMed]

99.

Richner JM, Himansu S, Dowd KA, Butler SL, Salazar V, Fox JM, et al. Modified mRNA Vaccines Protect against Zika Virus Infection. Cell. 2017;168:1114–25.e10. [DOI] [PubMed] [PMC]

100.

Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature. 2017;543:248–51. [DOI] [PubMed] [PMC]

101.

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16:626–38. [DOI] [PubMed]

102.

Bouazzaoui A, Abdellatif AAH. Vaccine delivery systems and administration routes: Advanced biotechnological techniques to improve the immunization efficacy. Vaccine X. 2024;19:100500. [DOI] [PubMed] [PMC]

103.

Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol. 2012;12:592–605. [DOI] [PubMed]

104.

Criscuolo E, Caputo V, Diotti RA, Sautto GA, Kirchenbaum GA, Clementi N. Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines. J Immunol Res. 2019;2019:8303648. [DOI] [PubMed] [PMC]

105.

Pabst R. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)—Structure, function and species differences. Vaccine. 2015;33:4406–13. [DOI] [PubMed]

106.

Czerkinsky C, Holmgren J. Mucosal Delivery Routes for Optimal Immunization: Targeting Immunity to the Right Tissues. In: Kozlowski PA, editor. Mucosal Vaccines: Modern Concepts, Strategies, and Challenges. Berlin, Heidelberg: Springer Berlin Heidelberg; 2012. pp. 1–18. [DOI] [PubMed]

107.

Cohen D, Muhsen K. Vaccines for enteric diseases. Hum Vaccin Immunother. 2019;15:1205–14. [DOI] [PubMed] [PMC]

108.

Menon I, Bagwe P, Gomes KB, Bajaj L, Gala R, Uddin MN, et al. Microneedles: A New Generation Vaccine Delivery System. Micromachines (Basel). 2021;12:435. [DOI] [PubMed] [PMC]

109.

Snapper CM. Distinct Immunologic Properties of Soluble Versus Particulate Antigens. Front Immunol. 2018;9:598. [DOI] [PubMed] [PMC]

110.

Goldwood G, Diesburg S. The effect of cool water pack preparation on vaccine vial temperatures in refrigerators. Vaccine. 2018;36:128–33. [DOI] [PubMed] [PMC]

111.

Filipić B, Pantelić I, Nikolić I, Majhen D, Stojić-Vukanić Z, Savić S, et al. Nanoparticle-Based Adjuvants and Delivery Systems for Modern Vaccines. Vaccines (Basel). 2023;11:1172. [DOI] [PubMed] [PMC]

112.

Bezbaruah R, Chavda VP, Nongrang L, Alom S, Deka K, Kalita T, et al. Nanoparticle-Based Delivery Systems for Vaccines. Vaccines (Basel). 2022;10:1946. [DOI] [PubMed] [PMC]

113.

Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021;6:1078–94. [DOI] [PubMed] [PMC]

114.

Grego EA, Siddoway AC, Uz M, Liu L, Christiansen JC, Ross KA, et al. Polymeric Nanoparticle-Based Vaccine Adjuvants and Delivery Vehicles. In: Gill HS, Compans RW, editors. Nanoparticles for Rational Vaccine Design. Cham: Springer International Publishing; 2021. pp. 29–76. [DOI] [PubMed] [PMC]

115.

Wang N, Chen M, Wang T. Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization. J Control Release. 2019;303:130–50. [DOI] [PubMed] [PMC]

116.

Bhardwaj P, Bhatia E, Sharma S, Ahamad N, Banerjee R. Advancements in prophylactic and therapeutic nanovaccines. Acta Biomater. 2020;108:1–21. [DOI] [PubMed] [PMC]

117.

He J, Yu L, Lin X, Liu X, Zhang Y, Yang F, et al. Virus-like Particles as Nanocarriers for Intracellular Delivery of Biomolecules and Compounds. Viruses. 2022;14:1905. [DOI] [PubMed] [PMC]

118.

Gajbhiye KR, Salve R, Narwade M, Sheikh A, Kesharwani P, Gajbhiye V. Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics. Mol Cancer. 2023;22:160. [DOI] [PubMed] [PMC]

119.

Quantitative risk assessment of the effects of climate change on selected causes of death, 2030s and 2050s [Internet]. WHO; c2020 [cited 2025 Feb 26]. Available from: https://iris.who.int/handle/10665/134014

120.

Immunization Agenda 2030: A Global Strategy To Leave No One Behind [Internet]. WHO; c2025 [cited 2025 Feb 26]. Available from: https://www.who.int/publications/m/item/immunization-agenda-2030-a-global-strategy-to-leave-no-one-behind

121.

Trovato M, Sartorius R, D’Apice L, Manco R, De Berardinis P. Viral Emerging Diseases: Challenges in Developing Vaccination Strategies. Front Immunol. 2020;11:2130. [DOI] [PubMed] [PMC]

122.

Lubanga AF, Bwanali AN, Kangoma M, Matola Y, Moyo C, Kaonga B, et al. Addressing the re-emergence and resurgence of vaccine-preventable diseases in Africa: A health equity perspective. Hum Vaccin Immunother. 2024;20:2375081. [DOI] [PubMed] [PMC]

123.

Coccia M. Improving preparedness for next pandemics: Max level of COVID-19 vaccinations without social impositions to design effective health policy and avoid flawed democracies. Environ Res. 2022;213:113566. [DOI] [PubMed] [PMC]

124.

Kennedy RB, Ovsyannikova IG, Palese P, Poland GA. Current Challenges in Vaccinology. Front Immunol. 2020;11:1181. [DOI] [PubMed] [PMC]

125.

Rodrigues F, Ziade N, Jatuworapruk K, Caballero-Uribe CV, Khursheed T, Gupta L. The Impact of Social Media on Vaccination: A Narrative Review. J Korean Med Sci. 2023;38:e326. [DOI] [PubMed] [PMC]

126.

Dubé E, Laberge C, Guay M, Bramadat P, Roy R, Bettinger J. Vaccine hesitancy: an overview. Hum Vaccin Immunother. 2013;9:1763–73. [DOI] [PubMed] [PMC]

127.

Tuckerman J, Kaufman J, Danchin M. Effective Approaches to Combat Vaccine Hesitancy. Pediatr Infect Dis J. 2022;41:e243–5. [DOI] [PubMed] [PMC]

128.

Larson HJ, Gakidou E, Murray CJL. The Vaccine-Hesitant Moment. N Engl J Med. 2022;387:58–65. [DOI] [PubMed] [PMC]

129.

National Academies of Sciences, Engineering, and Medicine. Public–Private Partnership Responses to COVID-19 and Future Pandemics: Proceedings of a Workshop—in Brief. Casola L, editor. Washington, DC: The National Academies Press; 2020. [DOI]

130.

Mackenzie JS, Drury P, Arthur RR, Ryan MJ, Grein T, Slattery R, et al. The global outbreak alert and response network. Glob Public Health. 2014;9:1023–39. [DOI] [PubMed] [PMC]

131.

Olatunji AO, Olaboye JA, Maha CC, Kolawole TO, Abdul S. Emerging vaccines for emerging diseases: Innovations in immunization strategies to address global health challenges. Int Med Sci Res J. 2024;4:740–55. [DOI]

132.

Constance Obiuto N, Adekola Adebayo R, Kayode Olajiga O, Clinton Festus-Ikhuoria I. Integrating Artificial Intelligence in Construction Management: Improving Project Efficiency and Cost-effectiveness. Int J Adv Multidisc Res Stud. 2024;4:639–47.

133.

Coccia M, Benati I. Effective health systems facing pandemic crisis: lessons from COVID-19 in Europe for next emergencies. Int J Health Governance. 2024;29:89–111. [DOI]

134.

Coccia M. Optimal levels of vaccination to reduce COVID-19 infected individuals and deaths: A global analysis. Environ Res. 2022;204:112314. [DOI] [PubMed] [PMC]

135.

O’Brien KL, Lemango E, Nandy R, Lindstrand A. The immunization Agenda 2030: A vision of global impact, reaching all, grounded in the realities of a changing world. Vaccine. 2024;42:S1–4. [DOI] [PubMed] [PMC]

136.

Orenstein WA, Offit PA, Edwards KM, Plotkin SA. Plotkin’s Vaccines. 8th ed. Elsevier; 2023. [DOI]

137.

Stern AM, Markel H. The history of vaccines and immunization: familiar patterns, new challenges. Health Aff (Millwood). 2005;24:611–21. [DOI] [PubMed]

138.

Greenwood B. The contribution of vaccination to global health: past, present and future. Philos Trans R Soc Lond B Biol Sci. 2014;369:20130433. [DOI] [PubMed] [PMC]

139.

Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261–79. [DOI] [PubMed] [PMC]

140.

Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid Nanoparticles—From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS Nano. 2021;15:16982–7015. [DOI] [PubMed]

141.

Omer SB, Salmon DA, Orenstein WA, deHart MP, Halsey N. Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases. N Engl J Med. 2009;360:1981–8. [DOI] [PubMed]

142.

Peek LJ, Middaugh CR, Berkland C. Nanotechnology in vaccine delivery. Adv Drug Deliv Rev. 2008;60:915–28. [DOI] [PubMed] [PMC]