Image of mRNA

Different types of vaccine

The broad range of vaccine delivery platforms

Vaccines are biological products that can induce an immune response and confer protection against infection or disease using a variety of technologies and platforms.1

Classification of vaccines is based on their constituents and mechanism of action, with a broad binary grouping being ‘live’ versus ‘non-live’ vaccines.1 Innovations in vaccine design in the past century have driven the discovery and development of new platforms to deliver vaccines.1,2

A range of vaccine delivery platforms are in use today:2-6

Illustrated diagram depicting different types of vaccine. Whole-cell vaccines, which include inactivated and live attenuated vaccines; and component vaccines, which includes subunit, toxoid, viral vector and mRNA vaccines.

Considering advantages and limitations of different vaccines

Different vaccines targeting the same pathogen can employ different technologies, each with their own advantages and limitations.2 Relevant considerations include the following:

  • Mechanism and degree of protection

    Depending on the biology of the infection and the disease being prevented, a vaccine may require induction of humoral or cell-mediated responses to be successful, with considerations including the following:2

    • Does the vaccine mimic natural infection?2
    • Is the native antigen preserved in the vaccine? Does the production process (e.g. inactivation) alter the immunogenic components?2
    • How robust is the stimulated immune response?2
    • Is the immune response skewed more towards innate or adaptive immunity, or does the vaccine induce both?2

  • Impact on suitability for different patients

    Some vaccines, particularly live vaccines, are contraindicated in certain groups, including:7

    • Individuals with a history of confirmed anaphylactic reaction to a previous dose of the vaccine or a component of the vaccine
    • Individuals with inborn errors of immunity or acquired immunodeficiency
    • Individuals recently or currently receiving immunosuppressive or immunosuppressive biological therapy, or infants born to mothers who received such treatment during pregnancy
    • Pregnant women
    • Those in close contact with an individual who is immunocompromised

    Certain populations, such as infants, older adults or immunocompromised individuals, may have weaker immune responses to vaccines than other populations. Adjuvanted vaccines can be particularly useful in these groups as addition of an adjuvant can enhance the immune response.2

  • Disease elimination strategy

    While vaccines are usually intended to prevent clinical manifestation of disease in individuals, immunisation programmes with some vaccines can provide a broader form of protection for populations too:1,2

    • Does the vaccine protect against asymptomatic infection of individuals, reducing carriage of the pathogen and onward transmission within a population?1
    • By limiting the risk of exposure for individuals, does the vaccine provide indirect protection of unvaccinated individuals in the population – i.e. does it provide herd immunity?1,2

  • Logistical aspects

    Logistical considerations relating to manufacturing and distribution can vary by vaccine type:1,2,3

    • Is production scalable? Is there a need to generate large quantities of vaccine in a time-effective manner?1,2,3
      • During the COVID-19 pandemic, mRNA vaccines were important in their ability to be scaled up to meet global needs3,5,8
    • Is the vaccine stable and long-lasting in storage?1,2

Find out more

What is an adjuvanted vaccine?

Read more about adjuvants and how they work

Recent advances in vaccine technologies

Significant advances in the fields of immunology and vaccinology in the past half-century have enabled the development of novel vaccine design and delivery platforms.8,9 The emergence of the COVID-19 pandemic also provided a significant boost to vaccine development and research.8

Viral vector vaccines

Icon of a virus

Viral vector vaccines are recombinant viruses.1,2,5,8 A non-pathogenic viral vector, such as a weakened adenovirus, is genetically engineered to include genes coding for antigenic proteins of the disease-causing pathogen of interest. The vector acts as a carrier and can be replicating or non‑replicating.1,5

The stimulus provided by viral vector vaccines mimics natural infection and leads to a strong humoral and cellular immune response, often without the need for additional components (or adjuvants) to enhance this.1,5

An introduction to viral vector vaccines

Nucleic acid vaccines

Icon of DNA

Nucleic acid vaccines consist of either DNA or mRNA that codes for the target antigen.1 While DNA vaccines have faced limitations due to a need to cross the nuclear membrane, newer technologies such as electroporation and jet injectors have been investigated to enhance delivery.5

mRNA vaccines have gained significantly more attention than DNA vaccines – whereas DNA vaccines need to be transcribed to mRNA in the nucleus, mRNA can be immediately translated within the cell cytoplasm.3,5 These vaccines are highly versatile and can be produced for emerging pathogens quickly and easily, as showcased during the COVID-19 pandemic, with the first mRNA vaccine approved for use in humans.1,5

Biomaterial-based vaccines

Icon of a lipid nanoparticle

New technologies are being explored to make carriers of vaccines more effective. Lipid nanoparticles, for example, have been used in SARS-CoV-2 vaccines to effectively protect and transport mRNA into cells.10

Other advancements such as tethering to spherical carriers, like gold nanoparticles, enhance immunogenicity and minimise off-target effects.5 Polymer chemistry can also be exploited to drive in situ expression of the antigen and manipulate the kinetics of immune responses, in contrast to traditional vaccines that are delivered as a bolus injection.5

Reverse vaccinology

Reverse vaccinology is a new technique that allows the identification of target antigens that may not be discovered by traditional means; it involves the cloning and expression of all proteins in a pathogen’s genome sequence predicted by computer algorithms to be exposed on their surface or excreted.11,12 Reverse vaccinology has enabled researchers to overcome some of the limitations of conventional vaccine development approaches.12

An overview of reverse vaccinology

The future of vaccines

As our understanding of immunology progresses, there is a need to develop new vaccine designs to address unmet needs and improve already existing vaccines.2 Vaccines of the future could provide innovation in different ways:

  • Addressing pathogen factors2

    • Could multiple serotypes of the pathogen be targeted?
    • Is there antigenic hypervariability in the pathogen that cannot be addressed with a single vaccine design?
    • Does the pathogen have an intracellular phase that is predominantly controlled by T‑cell responses?
      • Inducing a protective T-cell response in the right location has been a challenge in translating vaccine design from animal studies to human trials13

    • What is the impact of pre-existing immunity to vaccine technologies such as viral vectors?
      • Pre-existing immunity to human adenovirus vectors can result in reduced efficacy, but simian adenoviruses offer an alternative solution1
    • Can the vaccine be administered via another route, such as an intranasal, oral or sublingual route?

References

  1. Pollard AJ and Bijker EM. A guide to vaccinology: From basic principles to new developments. Nat Rev Immunol 2021;21:83–100.
  2. Vetter V et al. Understanding modern-day vaccines: What you need to know. Ann Med 2018;50:110120.
  3. Kozak M and Hu J. The integrated consideration of vaccine platforms, adjuvants, and delivery routes for successful vaccine development. Vaccines (Basel) 2023;11:695.
  4. Travieso T et al. The use of viral vectors in vaccine development. NPJ Vaccines 2022;7:75.
  5. Gebre MS et al. Novel approaches for vaccine development. Cell 2021;184:1589–1603.
  6. U.S. Department of Health and Human Services. Vaccine types. https://www.hhs.gov/immunization/basics/types/index.html (accessed February 2024).
  7. UK Health Security Agency. Contraindications and special considerations: The Green Book, chapter 6 (August 2017). https://assets.publishing.service.gov.uk/media/5a82ce28e5274a2e8ab5970f/Greenbook_chapter_6.pdf (accessed February 2024).
  8. Matic Z and Santak M. Current view on novel vaccine technologies to combat human infectious diseases. Appl Microbiol Biotechnol 2022;106:25–56.
  9. Tripathi T. Advances in vaccines: Revolutionizing disease prevention. Sci Rep 2023;13:11748.
  10. Tenchov R et al. Lipid nanoparticles — From liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 2021;15:16982–17015.
  11. Delany I et al. Vaccines, reverse vaccinology, and bacterial pathogenesis. Cold Spring Harb Perspect Med 2013;3:a012476.
  12. Seib KL et al. Developing vaccines in the era of genomics: a decade of reverse vaccinology. Clin Microbiol Infect 2012;18 Suppl 5:109-116.
  13. Griffiths KL and Khader SA. Novel vaccine approaches for protection against intracellular pathogens. Curr Opin Immunol 2014;28:58-63.

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June 2024 | NP-GB-ABX-WCNT-240003 (V1.0)