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inactivated vaccine

{{short description|Vaccine using a killed version of a disease pathogen}}

{{see also|Vaccination schedule|Vaccination policy#By country}}

{{Infobox medical intervention (new)

| name = Inactivated vaccine

| synonyms = Killed vaccine

Non-replicating vaccines

| image = Soldiers receiving typhoid vaccinations (Reeve 036335), National Museum of Health and Medicine (5243638771).jpg

| caption = Typhoid prophylaxis for soldiers in World War I.

| alt =

| pronounce =

| specialty = Public health, Immunology, Family medicine, General practice

| uses = prevention of infectious diseases

| complications =

| approach =

| types =

| recovery time =

| other options =

| outcomes = development of active immunity in individuals; contribution to herd immunity

| frequency = birth to adulthood | cost =

}}

An inactivated vaccine (or killed vaccine) is a type of vaccine that contains pathogens (such as virus or bacteria) that have been killed or rendered inactive, so they cannot replicate or cause disease. In contrast, live vaccines use pathogens that are still alive (but are almost always attenuated, that is, weakened). Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent infection from the vaccine.{{cite journal |vauthors=Petrovsky N, Aguilar JC |title=Vaccine adjuvants: current state and future trends |journal=Immunology and Cell Biology |volume=82 |issue=5 |pages=488–496 |date=October 2004 |pmid=15479434 |doi=10.1111/j.0818-9641.2004.01272.x |s2cid=154670}}

Inactivated vaccines were first developed in the late 1800s and early 1900s for cholera, plague, and typhoid.{{cite journal |vauthors=Plotkin SA, Plotkin SL |title=The development of vaccines: how the past led to the future |journal=Nature Reviews. Microbiology |volume=9 |issue=12 |pages=889–893 |date=October 2011 |pmid=21963800 |doi=10.1038/nrmicro2668 |s2cid=32506969 |publication-date=2011-10-03 |doi-access=free}} In 1897, Japanese scientists developed an inactivated vaccine for the bubonic plague. In the 1950s, Jonas Salk created an inactivated vaccine for the poliovirus, creating the first vaccine that was both safe and effective against polio. Today, inactivated vaccines exist for many pathogens, including influenza, polio (IPV), rabies, hepatitis A, CoronaVac, Covaxin and pertussis.{{cite book |vauthors=Wodi AP, Morelli V |chapter=Chapter 1: Principles of Vaccination |veditors=Hall E, Wodi AP, Hamborsky J, Morelli V, Schilllie S |title=Epidemiology and Prevention of Vaccine-Preventable Diseases |year=2021 |edition=14th |chapter-url= https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf |url=https://www.cdc.gov/vaccines/pubs/pinkbook/index.html |location=Washington, D.C. |publisher=Public Health Foundation, Centers for Disease Control and Prevention}}{{Cite book |last=Brown |first=Jonathan |title=The History of Medicine: A Scandalously Short Introduction |date=1997 |publisher=W.W. Norton & Company |isbn=978-0-393-31611-7 |edition=1st |publication-date=1997 |pages=1–530 |language=en}}

Because inactivated pathogens tend to produce a weaker response by the immune system than live pathogens, immunologic adjuvants and multiple "booster" injections may be required in some vaccines to provide an effective immune response against the pathogen.{{cite web|last1=WHO Expert Committee on Biological Standardization |title=Influenza |date=19 June 2019 |url=https://www.who.int/teams/health-product-and-policy-standards/standards-and-specifications/vaccine-standardization/influenza |publisher=World Health Organization (WHO) |access-date=22 October 2021}}{{cite web|title=Types of Vaccines |url=http://www.vaccines.gov/more_info/types/|website=Vaccines.gov |publisher=U.S. Department of Health and Human Services|access-date=16 May 2016 |date=23 July 2013|archive-url=https://web.archive.org/web/20130609071759/http://www.vaccines.gov/more_info/types|archive-date=9 June 2013}} Attenuated vaccines are often preferable for generally healthy people because a single dose is often safe and very effective. However, some people cannot take attenuated vaccines because the pathogen poses too much risk for them (for example, elderly people or people with immunodeficiency). For those patients, an inactivated vaccine can provide protection.{{citation needed|date=July 2023}}

Mechanism

The pathogen particles are destroyed and cannot divide, but the pathogens maintain some of their integrity to be recognized by the immune system and evoke an adaptive immune response.{{cite journal |vauthors = Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M |title=Understanding modern-day vaccines: what you need to know |journal=Annals of Medicine |volume=50 |issue=2 |pages=110–120 |date=March 2018 |pmid=29172780 |doi=10.1080/07853890.2017.1407035 |s2cid=25514266 |doi-access=free}}{{cite journal |vauthors=Slifka MK, Amanna I |title=How advances in immunology provide insight into improving vaccine efficacy |journal=Vaccine |volume=32 |issue=25 |pages=2948–2957 |date=May 2014 |pmid=24709587 |pmc=4096845 |doi=10.1016/j.vaccine.2014.03.078}} When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles.{{Citation needed|date=November 2021|reason=No citation previously given, may be confusing given that properly inactivated vaccines cannot cause disease}}

When a vaccine is administered, the antigen will be taken up by an antigen-presenting cell (APC) and transported to a draining lymph node in vaccinated people. The APC will place a piece of the antigen, an epitope, on its surface along with a major histocompatibility complex (MHC) molecule. It can now interact with and activate T cells. The resulting helper T cells will then stimulate an antibody-mediated or cell-mediated immune response and develop an antigen-specific adaptive response.{{cite journal |vauthors=Pollard AJ, Bijker EM |title=A guide to vaccinology: from basic principles to new developments |journal=Nature Reviews. Immunology |volume=21 |issue=2 |pages=83–100 |date=February 2021 |pmid=33353987 |pmc=7754704 |doi=10.1038/s41577-020-00479-7}}{{cite journal |vauthors=Karch CP, Burkhard P |title=Vaccine technologies: From whole organisms to rationally designed protein assemblies |journal=Biochemical Pharmacology |volume=120 |pages=1–14 |date=November 2016 |pmid=27157411 |pmc=5079805 |doi=10.1016/j.bcp.2016.05.001}} This process creates an immunological memory against the specific pathogen and allows the immune system to respond more effectively and rapidly after subsequent encounters with that pathogen.

Inactivated vaccines tend to produce an immune response that is primarily antibody-mediated. However, deliberate adjuvant selection allows inactivated vaccines to stimulate a more robust cell-mediated immune response.

Social Consequences

The use of inactivated vaccines helped reduce morbidity and mortality from diseases like tetanus, diphtheria, and pertussis, creating a healthier, more stable society. Community health improved as a result, particularly in developed nations, where high vaccination rates led to herd immunity.{{cite book |last1=Oshinsky |first1=David M. |title=Polio: An American Story |date=2005 |publisher=Oxford University Press |isbn=978-0-19-515294-4 |title-link=Polio: An American Story }}{{page needed|date=November 2024}}

Reducing diseases like polio, hepatitis A, and influenza meant fewer people suffering from debilitating illness, which in turn led to increased social productivity. Families no longer had to care for loved ones with debilitating diseases, and children could go to school without the constant fear of contraction. Inactivated vaccines increased public trust in public health systems, normalizing vaccinations to the point where yearly flu shots and childhood immunization are seen as routine parts of life, especially in developed countries.

Types

Inactivated vaccines can be divided by the method used for killing the pathogen.

  • Whole pathogen inactivated vaccines are produced when an entire pathogen is 'killed' using heat, chemicals, or radiation, although only formaldehyde and beta-Propiolactone exposure are widely used in human vaccines.{{cite book | vauthors = Sanders B, Koldijk M, Schuitemaker H | title = Vaccine Analysis: Strategies, Principles, and Control | chapter = Inactivated Viral Vaccines | pmc = 7189890 |date=2015 |pages=45–80 |doi=10.1007/978-3-662-45024-6_2 |isbn=978-3-662-45023-9 |s2cid=81212732 }}{{cite journal |last1=Hotez |first1=Peter J. |last2=Bottazzi |first2=Maria Elena |title=Whole Inactivated Virus and Protein-Based COVID-19 Vaccines |journal=Annual Review of Medicine |date=27 January 2022 |volume=73 |issue=1 |pages=55–64 |doi=10.1146/annurev-med-042420-113212 |pmid=34637324 |s2cid=238747462 |issn=0066-4219|doi-access=free }}
  • Split virus vaccines are produced by using a detergent to disrupt the viral envelope.{{cite journal | vauthors = Chen J, Wang J, Zhang J, Ly H | title = Advances in Development and Application of Influenza Vaccines | journal = Frontiers in Immunology | volume = 12 | pages = 711997 | date = 2021 | pmid = 34326849 | pmc = 8313855 | doi = 10.3389/fimmu.2021.711997 | doi-access = free }} This technique is used in the development of many influenza vaccines.{{cite journal | vauthors=Gemmill I, Young K |collaboration=National Advisory Committee on Immunization (NACI) | title=Summary of the NACI literature review on the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in older adults | journal=Can Commun Dis Rep | volume=44 | issue=6 | pages=129–133 | doi=10.14745/ccdr.v44i06a02 | date=May 2018 | url=https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2018-44/issue-6-june-7-2018/article-2-summary-subunit-split-virus-influenza-vaccine.html | pmc=6449119 }}

A minority of sources use the term inactivated vaccines to broadly refer to non-live vaccines. Under this definition, inactivated vaccines also include subunit vaccines and toxoid vaccines.

Examples

Types include:{{cite book | vauthors = Ghaffar A, Haqqi T | chapter-url=http://pathmicro.med.sc.edu/ghaffar/immunization-ver2.htm | archive-url = https://web.archive.org/web/20140226142347/http://pathmicro.med.sc.edu/ghaffar/immunization-ver2.htm | archive-date = 26 February 2014 | chapter = Immunization | title = Immunology | publisher = The Board of Trustees of the University of South Carolina |access-date=2009-03-10}}

Advantages and disadvantages

= Advantages =

  • Inactivated pathogens are more stable than live pathogens. Increased stability facilitates the storage and transport of inactivated vaccines.{{cite journal |vauthors=Clem AS |title=Fundamentals of vaccine immunology |journal=Journal of Global Infectious Diseases |volume=3 |issue=1 |pages=73–78 |date=January 2011 |pmid=21572612 |pmc=3068582 |doi=10.4103/0974-777X.77299 |doi-access=free}}{{Cite web |title=Inactivated whole-cell (killed antigen) vaccines - WHO Vaccine Safety Basics |url=https://vaccine-safety-training.org/inactivated-whole-cell-vaccines.html|access-date=2021-11-11 |website=vaccine-safety-training.org |publisher=World Health Organization (WHO)}}
  • Unlike live attenuated vaccines, inactivated vaccines cannot revert to a virulent form and cause disease.{{cite book |doi=10.1016/B978-0-323-79058-1.00067-0 |chapter=Technologies for Making New Vaccines |title=Plotkin's Vaccines |date=2023 |last1=Pecetta |first1=Simone |last2=Ahmed |first2=S. Sohail |last3=Ellis |first3=Ronald |last4=Rappuoli |first4=Rino |pages=1350–1373.e9 |isbn=978-0-323-79058-1 }} For example, there have been rare instances of the live attenuated form of poliovirus present in the oral polio vaccine (OPV) becoming virulent, leading to the inactivated polio vaccine (IPV) replacing OPV in many countries with controlled wild-type polio transmission.
  • Unlike live attenuated vaccines, inactivated vaccines do not replicate and are not contraindicated for immunocompromised individuals.

= Disadvantages =

  • Inactivated vaccines have a reduced ability to produce a robust immune response for long-lasting immunity when compared to live attenuated vaccines. Adjuvants and boosters are often required to produce and maintain protective immunity.
  • Pathogens must be cultured and inactivated for the creation of killed whole-organism vaccines. This process slows down vaccine production when compared to genetic vaccines.
  • Inactivated vaccines tend to produce less durable immunity, often requiring multiple doses, which can pose a public health challenge. For example, the flu vaccine requires annual updates and re-administration, and hepatitis A vaccines often require two doses spaced six months apart.

References

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{{Vaccines}}