Nanovaccines and the History of Vaccinology

  • Sergio Rosales-Mendoza
  • Omar González-Ortega


Vaccines have been historically linked to prominent benefits for global health. The concept of vaccination was first recorded in Asia and subsequently consolidated by the better documented studies by Jenner and Pasteur during the eighteenth and nineteenth centuries. Later, mainly in the twentieth century, the design and production of vaccines were expanded to massively apply vaccines in the benefit of human and animal health, being prominently based on whole killed or attenuated bacteria or viruses. Next generation (subunit) vaccines based on few antigens and possibly some adjuvants have been proposed as the ideal vaccination approach since the risks (strain reversion to pathogenic forms, high reactogenicity, and expensive manufacture, among others) associated with the use of whole pathogens are avoided. The development of toxoids and the use of polysaccharide conjugates added an important piece to the vaccinology portfolio, leading to the first subunit vaccines; however, the application of these approaches in the clinic is only beginning and myriad efforts are ongoing to expand their use. Nanosized vaccines are a promise in this field since nanomaterials offer singular properties that may enhance the efficacy of subunit vaccines, thus resulting in innovative vaccines. Genetic engineering has made possible to introduce nanosized vaccines (based on virus-like particles) in the market, which target the hepatitis B virus and human papillomavirus and are produced in well-established platforms, namely recombinant yeasts and insect cells. Innovative recombinant platforms offering low cost and other advantages are under development; these include plant cells and algae, among others. Besides protein-based nanoparticles, the nanotechnology field offers a wide range of nanomaterials to be applied for vaccine nanotechnology that include metallic and polymeric nanoparticles, nanogels, carbon nanomaterials, and liposomes. A substantial progress in the vaccinology field is envisioned as a consequence of the application of such nanomaterials in the vaccinology field, especially on the development of mucosal vaccines.


Vaccine Subunit vaccine Toxoids Conjugate vaccine Nanomaterials Virus-like particles Mucosal vaccine 


  1. Ajithkumar KC, Pramod K (2018) Artificial virus as trump-card to resolve exigencies in targeted gene delivery. Mini Rev Med Chem 18(3):276–286CrossRefGoogle Scholar
  2. Atluri R, Jensen KA (2017) Engineered nanomaterials: their physicochemical characteristics and how to measure them. Adv Exp Med Biol 947:3–23CrossRefGoogle Scholar
  3. Avery OT, Goebel WF (1929) Chemo-immunological studies on conjugated carbohydrate-proteins. II. Immunological specificity of synthetic sugar-proteins. J Exp Med 50:521–533CrossRefGoogle Scholar
  4. Baker PJ (1992) T cell regulation of the antibody response to bacterial polysaccharide antigens: an examination of some general characteristics and their implications. J Infect Dis 165(Suppl. 1):S44–S48CrossRefGoogle Scholar
  5. Barber DJ, Freestone IC (1990) An investigation of the origin of the color of the Lycurgus cup by analytical transmission electron-microscopy. Archaeometry 32:33–45CrossRefGoogle Scholar
  6. Booy R, Hodgson S, Carpenter L, Mayon-White RT, Slack MP, Macfarlane JA, Haworth EA, Kiddle M, Shribman S, Roberts JS et al (1994) Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T. Lancet 344:362–366CrossRefGoogle Scholar
  7. Cabral GA, Marciano-Cabral F, Funk GA, Sanchez Y, Hollinger FB, Melnick JL, Dreesman GR (1978) Cellular and humoral immunity in Guinea pigs to two major polypeptides derived from hepatitis B surface antigen. J Gen Virol 38:339–350CrossRefGoogle Scholar
  8. Cadeddu A (1985) Pasteur et le choléra des poules: révision critique d’un récit historique. Historical Philosophical Life Science 7:87–104Google Scholar
  9. Calmette A, Guérin C (1909) Sur quelques propriétés du bacilli tuberculeux d’origine bovine cultivé sur bile de boeuf glycérinée. CR Acad Sci 150:716–718Google Scholar
  10. Calmette A, Guérin C (1931) Nouvelles recherches expérimentales sur la vaccination des bovidés contre la tuberculose et sur le sort du bacilli tuberculeux dans l’organisme de vaccinés. Ann Inst Pasteur 27:162–169Google Scholar
  11. Casanova I, Unzueta U, Arroyo-Solera I, Céspedes MV, Villaverde A, Mangues R, Vazquez E (2019) Protein-driven nanomedicines in oncotherapy. Curr Opin Pharmacol 47:1–7CrossRefGoogle Scholar
  12. Cho EY, Ryu JY, Lee HAR, Hong SH, Park HS, Hong KS, Park SG, Kim HP, Yoon TJ (2019) Lecithin nano-liposomal particle as a CRISPR/Cas9 complex delivery system for treating type 2 diabetes. J Nanobiotechnology 17(1):19CrossRefGoogle Scholar
  13. Cohen SN, Chang AC, Boyer HW, Helling RB (1973) Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci U S A 70(11):3240–3244CrossRefGoogle Scholar
  14. Dandolos E, Roumeliotou-Karayannis A, Richardson SC, Papaevangelou G (1985) Safety and immunogenicity of a recombinant hepatitis B vaccine. J Med Virol 17(1):57–62CrossRefGoogle Scholar
  15. Eckert M (2012) Max von Laue and the discovery of X-ray diffraction in 1912. Ann Phys 524(5):A83–A85CrossRefGoogle Scholar
  16. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID (1988) Smallpox and its eradication. World Health Organization 560, GenevaGoogle Scholar
  17. Fredriksen BN, Grip J (2012) PLGA/PLA micro- and nanoparticle formulations serve as antigen depots and induce elevated humoral responses after immunization of Atlantic salmon (Salmo salar L.). Vaccine 30:656–667CrossRefGoogle Scholar
  18. Freestone I, Meeks N, Sax M, Higgitt C (2007) The Lycurgus cup – a Roman nanotechnology. Gold Bull 40(4):270–277CrossRefGoogle Scholar
  19. Goldblatt D (2000) Conjugate vaccines. Clin Exp Immunol 119(1):1–3CrossRefGoogle Scholar
  20. Harper DM, DeMars LR (2017) HPV vaccines - a review of the first decade. Gynecol Oncol 146(1):196–204CrossRefGoogle Scholar
  21. He Y, Hara H, Núñez G (2016) Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41:1012–1021CrossRefGoogle Scholar
  22. Jelinek T, Kollaritsch H (2008) Vaccination with Dukoral against travelers’ diarrhea (ETEC) and cholera. Expert Rev Vaccines 7(5):561–567CrossRefGoogle Scholar
  23. Jilg W, Schmidt M, Zoulek G, Lorbeer B, Wilske B, Deinhardt F (1984) Clinical evaluation of a recombinant hepatitis B vaccine. Lancet 324:1174–1175CrossRefGoogle Scholar
  24. Karch CP, Burkhard P (2016) Vaccine technologies: from whole organisms to rationally designed protein assemblies. Biochem Pharmacol 120:1–14CrossRefGoogle Scholar
  25. Mamo T, Poland GA (2012) Nanovaccinology: the next generation of vaccines meets 21st century materials science and engineering. Vaccine 30:6609–6611CrossRefGoogle Scholar
  26. Martinón-Torres F, Heininger U, Thomson A, Wirsing von König CH (2018) Controlling pertussis: how can we do it? A focus on immunization. Expert Rev Vaccines 17(4):289–297CrossRefGoogle Scholar
  27. Morrow JF, Cohen SN, Chang AC, Boyer HW, Goodman HM, Helling RB (1974) Replication and transcription of eukaryotic DNA in Escherichia coli. Proc Natl Acad Sci U S A 71(5):1743–1747CrossRefGoogle Scholar
  28. Moulin AM (1991) Le dernier langage de la medicine. In: Histoire de l’immunologie de Pasteur au sida. Presses universitaires de France, Paris, pp 21–22Google Scholar
  29. MRC (1951) Medical Research Council. The prevention of whooping-cough by vaccination. Br Med J 1:1463–1471CrossRefGoogle Scholar
  30. Nosova AS, Koloskova OO, Nikonova AA, Simonova VA, Smirnov VV, Kudlay D, Khaitov MR (2019) Diversity of PEGylation methods of liposomes and their influence on RNA delivery. Medchemcomm 10(3):369–377CrossRefGoogle Scholar
  31. Pachioni-Vasconcelos Jde A, Lopes AM, Apolinário AC, Valenzuela-Oses JK, Costa JS, Nascimento Lde O, Pessoa A, Barbosa LR, Rangel-Yagui Cde O (2016) Nanostructures for protein drug delivery. Biomater Sci 4:205–218CrossRefGoogle Scholar
  32. Pasteur L, Chamberland C, Roux E (1881) Le vaccin du charbon. CR Acad Sci 92:666–668Google Scholar
  33. Peltola H, Käyhty H, Sivonen A, Mäkelä PH (1977) Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 60:730–737Google Scholar
  34. Pfieffer R, Kolle W (1896) Experimentelle Untersuchungen zur Frage der Schutzimpfung des Menschen gegen Typhus abdominalis. Disch Med Wochenschr 22:735–737CrossRefGoogle Scholar
  35. Plotkin SA (2011) History of vaccine development. Springer, New YorkCrossRefGoogle Scholar
  36. Poland GA, Whitaker JA, Poland CM, Ovsyannikova IG, Kennedy RB (2016) Vaccinology in the third millennium: scientific and social challenges. Curr Opin Virol 17:116–125CrossRefGoogle Scholar
  37. Porter A, Goldfarb J (2019) Measles: a dangerous vaccine-preventable disease returns. Cleve Clin J Med 86(6):393–398CrossRefGoogle Scholar
  38. Qazi S, Miettinen HM, Wilkinson RA, McCoy K, Douglas T, Wiedenheft B (2016) Programmed self-assembly of an active P22-Cas9 nanocarrier system. Mol Pharm 13(3):1191–1196CrossRefGoogle Scholar
  39. Ramon G (1924a) On the properties of diphtheria toxoid. C R Hebd Acad Sci 179:422–425Google Scholar
  40. Ramon G (1924b) Toxoids. C R Hebd Acad Sci 178:1436–1439Google Scholar
  41. Ramon G (1925) Sur la production de l’antitoxine diphtérique. CR Soc Biol 93:508–509Google Scholar
  42. Relyveld EH (2011) A history of toxoids. In: Plotkin SA (ed) History of vaccine development. Springer, New YorkGoogle Scholar
  43. Rosales-Mendoza S, Angulo C, Meza B (2016) Food-grade organisms as vaccine biofactories and Oral delivery vehicles. Trends Biotechnol 34(2):124–136CrossRefGoogle Scholar
  44. Sabin AB, Hennessen WA, Winsser J (1954) Studies of variants of poliomyelitis virus. I. Experimental segregation and properties of avirulent variants of three immunologic types. J Exp Med 99:551–576CrossRefGoogle Scholar
  45. Salk JE, Bazeley PL, Bennett BL, Krech U, Lewis LJ, Ward EN, Youngner JS (1954) Studies in human subjects on active immunization against poliomyelitis. II. A practical means for inducing and maintaining antibody formation. Am J Public Health Nations Health 44(8):994–1009CrossRefGoogle Scholar
  46. Santosham M, Wolff M, Reid R, Hohenboken M, Bateman M, Goepp J, Cortese M, Sack D, Hill J, Newcomer W et al (1991) The efficacy in Navajo infants of conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. N Engl J Med 324:1767–1772CrossRefGoogle Scholar
  47. Schiller JT, Lowy DR (2011) Developmental history of HPV prophylactic vaccines. In: Plotkin SA (ed) History of vaccine development. Springer, New YorkGoogle Scholar
  48. Schonberger LB, Kaplan J, Kim-Farley R, Moore M, Eddins DL, Hatch M (2015) Control of paralytic poliomyelitis in the United States. Rev Infect Dis 6(Suppl 2):S424–S426Google Scholar
  49. Silva AL, Peres C, Conniot J, Matos AI, Moura L, Carreira B, Sainz V, Scomparin A, Satchi-Fainaro R, Préat V, Florindo HF (2017) Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation. Semin Immunol 34:3–24CrossRefGoogle Scholar
  50. Smith KA (2011) Edward Jenner and the small pox vaccine. Front Immunol 2:1–6CrossRefGoogle Scholar
  51. Szeto GL, Lavik EB (2016) Materials design at the interface of nanoparticles and innate immunity. J Mater Chem B 4(9):1610–1618CrossRefGoogle Scholar
  52. Ward J, Berkowitz C, Pescetti J (1984) Enhanced immunogenicity in young infants of a new Haemophilus influenzae type b capsular polysaccharide (PRP)-diphtheria toxoid (D) conjugate vaccine. Pediatr Res 18:287AGoogle Scholar
  53. WHO (2015) Immunization Systems Management Group of the Global Polio Eradication Initiative. Introduction of inactivated poliovirus vaccine and switch from trivalent to bivalent oral poliovirus vaccine - worldwide, 2013–2016. MMWR Morb Mortal Wkly Rep 64:699–702Google Scholar
  54. Wright AE, Semple D (1897) Remarks on vaccination against typhoid fever. Br Med J 1:256–259CrossRefGoogle Scholar
  55. Xingzhun (1953) Zhonggou yufang yixue sixiang shi (the history of medical thought on prevention in China). Shanghai, pp 106–110Google Scholar
  56. Zaman M, Good MF, Toth I (2013) Nanovaccines and their mode of action. Methods 60(3):226–231CrossRefGoogle Scholar
  57. Zhu M, Wang R, Nie G (2014) Applications of nanomaterials as vaccine adjuvants. Hum Vaccin Immunother 10:2761–2774CrossRefGoogle Scholar
  58. Zottel A, Videtič Paska A, Jovčevska I (2019) Nanotechnology meets oncology: nanomaterials in brain cancer research, diagnosis and therapy. Materials (Basel) 12(10). Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sergio Rosales-Mendoza
    • 1
  • Omar González-Ortega
    • 2
  1. 1.Facultad de Ciencias Químicas, Centro de Investigación en Ciencias de la Salud y BiomedicinaUniversidad Autónoma de San Luis PotosíSan Luis PotosíMexico
  2. 2.Facultad de Ciencias QuímicasUniversidad Autónoma de San Luis Potosí San Luis PotosíMexico

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