The Indian Journal of Pediatrics

, Volume 85, Issue 2, pp 132–138 | Cite as

Advances Towards Painless Vaccination and Newer Modes of Vaccine Delivery

  • Neha Garg
  • Anju Aggarwal
Review Article


Vaccines have been successful in reducing the mortality and morbidity, but most of them are delivered by intramuscular or intravenous route. They are associated with pain to the baby and bring lot of anxiety for the parents. There has been a marked increase in the number of injections required in first two years of life for completing the vaccination schedule. Hence, there is a need to have a painless vaccine delivery system. Numerous new routes of vaccination like, oral, nasal and transdermal routes are being tried. Oral polio and intranasal influenza have already been a success. Other newer approaches like edible vaccines, nasal sprays, dry powder preparations, jet injectors, microneedles and nanopatches are promising in delivering painless vaccines. Many of them are under clinical trials. These vaccine delivery systems will not only be painless but also cost effective, safe and easy to administer in mass population. They may be devoid of the need of cold chain. Painless delivery system will ensure better compliance to vaccination schedule.


Painless vaccination Needle-free vaccination Newer vaccine delivery 



The main manuscript was prepared by NG and it was revised by critical outputs from AA. AA will act as guarantor for the paper.

Compliance with Ethical Standards

Conflict of Interest


Source of Funding



  1. 1.
    World Health Organization. The expanded programme on immunization. Available at: . Accessed on 7th Jan 2017.
  2. 2.
    Vashishtha VM, Kumar P. 50 years of immunization in India: progress and future. Indian Pediatr. 2013;50:111–8.CrossRefPubMedGoogle Scholar
  3. 3.
    CDC Birth-18 Years Immunization Schedule. Available at: Accessed on 8th Jan 2017.
  4. 4.
    CDC Press Releases 2016. Available at: . Accessed on 27th Dec 2016.
  5. 5.
    Kennedy A, Basket M, Sheedy K. Vaccine attitudes, concerns, and information sources reported by parents of young children: results from the 2009 HealthStyles survey. Pediatrics. 2011;127:S92–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Taddio A, Ipp M, Thivakaran S, et al. Survey of the prevalence of immunization non-compliance due to needle fears in children and adults. Vaccine. 2012;30:4807–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Taddio A, Appleton M, Bortolussi R, et al. Reducing the pain of childhood vaccination: an evidence-based clinical practice guideline. Can Med Assoc J. 2010;182:E843–55.CrossRefGoogle Scholar
  8. 8.
    Halpert C, Meier S, Naus M. Reducing immunization injection pain in infants. BCMJ. 2015;57:189.Google Scholar
  9. 9.
    Eden LM, Macintosh JLB, Luthy KE, Beckstrand RL. Minimizing pain during childhood vaccination injections: improving adherence to vaccination schedules. Pediatric Health Med Ther. 2014;5:127–40.Google Scholar
  10. 10.
    Schechter NL, Zempsky WT, Cohen LL, McGrath PJ, McMurtry CM, Bright NS. Pain reduction during pediatric immunizations: evidence-based review and recommendations. Pediatrics. 2007;119:e1184–98.CrossRefPubMedGoogle Scholar
  11. 11.
    World Health Organization. Oral polio vaccine (OPV). Available at: . Accessed on 27th Dec 2016.
  12. 12.
    Giudice EL, Campbell JD. Needle-free vaccine delivery. Adv Drug Deliv Rev. 2006;58:68–89.CrossRefPubMedGoogle Scholar
  13. 13.
    Jackson BR, Iqbal S, Mahon B; Centers for Disease Control and Prevention (CDC). Updated recommendations for the use of typhoid vaccine--Advisory Committee on Immunization Practices, United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:305–8.Google Scholar
  14. 14.
    Saha A, Rosewell A, Hayen A, MacIntyre CR, Qadri F. Improving immunization approaches to cholera. Expert Rev Vaccines. 2017;16:235–48.CrossRefPubMedGoogle Scholar
  15. 15.
    Qadri F, Wierzba TF, Ali M, et al. Efficacy of a single-dose, inactivated oral cholera vaccine in Bangladesh. N Engl J Med. 2016;374:1723–32.CrossRefPubMedGoogle Scholar
  16. 16.
    Mason HS, Warzecha H, Mor T, Arntzen CJ. Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine. Trends Mol Med. 2002;8:324–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Jain A, Saini V, Kohli DV. Edible transgenic plant vaccines for different diseases. Curr Pharm Biotechnol. 2013;14:594–614.CrossRefPubMedGoogle Scholar
  18. 18.
    Chan H-T, Daniell H. Plant-made oral vaccines against human infectious diseases-are we there yet? Plant Biotechnol J. 2015;13:1056–70.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lal P, Ramachandran VG, Goyal R, Sharma R. Edible vaccines: current status and future. Indian J Med Microbiol. 2007;25:93–102.CrossRefPubMedGoogle Scholar
  20. 20.
    Czerkinsky C, Cuburu N, Kweon M-N, Anjuere F, Holmgren J. Sublingual vaccination. Hum Vaccin. 2011;7:110–4.CrossRefPubMedGoogle Scholar
  21. 21.
    Raghavan S, Östberg AK, Flach C-F, et al. Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach. Infect Immun. 2010;78:4251–60.Google Scholar
  22. 22.
    Lee H-J, Cho H, Kim M-G, et al. Sublingual immunization of trivalent human papilloma virus DNA vaccine in baculovirus nanovector for protection against vaginal challenge. PLoS One. 2015;10:e0119408.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kraan H, Vrieling H, Czerkinsky C, Jiskoot W, Kersten G, Amorij J-P. Buccal and sublingual vaccine delivery. J Control Release. 2014;190:580–92.CrossRefPubMedGoogle Scholar
  24. 24.
    Breath-fresh strips inspire new platform for vaccines. The Chemical Institute of Canada magazine September 2014. Available at: . Accessed on 10th Jan 2017.
  25. 25.
    Saroja C, Lakshmi P, Bhaskaran S. Recent trends in vaccine delivery systems: a review. Int J Pharm Investig. 2011;1:64–74.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Brain JD. Inhalation, deposition, and fate of insulin and other therapeutic proteins. Diabetes Technol Ther. 2007;9:S4–15.CrossRefPubMedGoogle Scholar
  27. 27.
    Birkhoff M, Leitz M, Marx D. Advantages of intranasal vaccination and considerations on device selection. Indian J Pharm Sci. 2009;71:729–31.PubMedCentralGoogle Scholar
  28. 28.
    CDC Vaccine Information Statement on Live Intranasal Influenza. Available at: . Accessed on 27th Dec 2016.
  29. 29.
    Makidon PE, Bielinska AU, Nigavekar SS, et al. Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine. PLoS One. 2008;3:e2954.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Suzuki H, Watari A, Hashimoto E, et al. C-Terminal Clostridium perfringens enterotoxin-mediated antigen delivery for nasal pneumococcal vaccine. PLoS One. 2015;10:e0126352.Google Scholar
  31. 31.
    Nantachit N, Sunintaboon P, Ubol S. Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination. Virol J. 2016;13:142.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Nasal spray vaccine has potential for long-lasting protection from Ebola virus. Science Daily. Available at: Accessed on 26th Dec 2016.
  33. 33.
    Thomas C, Gupta V, Ahsan F. Influence of surface charge of PLGA particles of recombinant hepatitis B surface antigen in enhancing systemic and mucosal immune responses. Int J Pharm. 2009;379:41–50.CrossRefPubMedGoogle Scholar
  34. 34.
    Lin W-H, Griffin DE, Rota PA, et al. Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques. Proc Natl Acad Sci U S A. 2011;108:2987–92.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lu D, Garcia-Contreras L, Muttil P, et al. Pulmonary immunization using antigen 85-B polymeric microparticles to boost tuberculosis immunity. AAPS J. 2010;12:338–47.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tonnis WF, Lexmond AJ, Frijlink HW, de Boer AH, Hinrichs WLJ. Devices and formulations for pulmonary vaccination. Expert Opin Drug Deliv. 2013;10:1383–97.CrossRefPubMedGoogle Scholar
  37. 37.
    Dilraj A, Cutts FT, de Castro JF, et al. Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren: a randomised trial. Lancet. 2000;355:798–803.CrossRefPubMedGoogle Scholar
  38. 38.
    Bennett JV. Fernandez de Castro J, Valdespino-Gomez JL, et al. Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren Bull World Health Organ. 2002;80:806–12.PubMedGoogle Scholar
  39. 39.
    Feng Z-X, Wei Y-N, Li G-L, et al. Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol vaccine. Vet Microbiol. 2013;167:417–24.CrossRefPubMedGoogle Scholar
  40. 40.
    Kim Y-C, Park J-H, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64:1547–68.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    McAllister DV, Wang PM, Davis SP, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A. 2003;100:13755–60.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Levin Y, Kochba E, Shukarev G, Rusch S, Herrera-Taracena G, van Damme P. A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly. Vaccine. 2016;34:5262–72.CrossRefPubMedGoogle Scholar
  43. 43.
    Behrens RH, Cramer JP, Jelinek T, et al. Efficacy and safety of a patch vaccine containing heat-labile toxin from Escherichia coli against travellers’ diarrhoea: a phase 3, randomised, double-blind, placebo-controlled field trial in travellers from Europe to Mexico and Guatemala. Lancet Infect Dis. 2014;14:197–204.CrossRefPubMedGoogle Scholar
  44. 44.
    Prow TW, Chen X, Prow NA, et al. Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice. Small Weinh Bergstr Ger. 2010;6:1776–84.Google Scholar
  45. 45.
    Fernando GJP, Chen X, Primiero CA, et al. Nanopatch targeted delivery of both antigen and adjuvant to skin synergistically drives enhanced antibody responses. J Control Release. 2012;159:215–21.CrossRefPubMedGoogle Scholar
  46. 46.
    CDC Flu Vaccination by Jet Injector Seasonal Influenza (Flu). Available at: Accessed on 16th Dec 2016.
  47. 47.
    Kim Y-C, Prausnitz MR. Enabling skin vaccination using new delivery technologies. Curr Top Microbiol Immunol. 2012;351:77–112.PubMedPubMedCentralGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2017

Authors and Affiliations

  1. 1.Department of PediatricsUniversity College of Medical Sciences and Guru Tegh Bahadur HospitalNew DelhiIndia

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