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Breakthrough infection

From Wikipedia, the free encyclopedia
See also:Vaccine resistance

Abreakthrough infectionis a case of illness in which a vaccinated individual becomes infected with the illness, because thevaccinehas failed to provide completeimmunityagainst thepathogen(currently onlyviruses).[1]Breakthrough infections have been identified in individuals immunized against a variety of diseases includingmumps,varicella (Chickenpox),influenza,andCOVID-19.[2][3][4]The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.[5]

Causes of breakthrough infections include biological factors in the recipient, improper administration or storage of vaccines, mutations in viruses,blocking antibodyformation, and other factors. For these reasons, vaccines are rarely 100% effective. A 2021 study found the common flu vaccine provided immunity to the flu in 58% of recipients.[6]Themeasles vaccinefails to provide immunity to 2% of children that receive the vaccine. However, ifherd immunityexists, it typically prevents individuals who are ineffectively vaccinated from contracting the disease.[7]Accordingly, herd immunity reduces the number of breakthrough infections in a population.[8]

By disease[edit]

Varicella[edit]

Thevaricella vaccineis 85% effective at preventingvaricella(chickenpox) infection.[9]However, 75% of individuals that are diagnosed with breakthrough varicella exhibit milder symptoms than individuals that are not vaccinated.[5]These individuals with mild varicella have low fevers, fewer than 50 lesions on their skin, and amaculopapular rash.In contrast, unvaccinated individuals typically have a fever of 102, 200-500 skin lesions, and macules (lesions that are not elevated) evolve topapulesand vesicular lesions.[5][10]Additionally, infection in unvaccinated individuals tends to last for a longer period of time than in individuals who have been vaccinated.[5]

The majority of cases of breakthrough varicella are attributed to the failure of an individual to uptake[clarification needed]the varicella vaccine.[9]Therefore, to prevent breakthrough infections, it is proposed that children receive a second dose of varicella vaccine less than a year after getting their first dose.[9]

Mumps[edit]

The mumps vaccine is a component of theMeasles, Mumps and Rubella vaccine(MMR).[11]The mumps vaccine, specifically, is 88% effective at preventing mumps.[12]Individuals with breakthrough cases of mumps have fewer serious complications from the infections as compared to individuals unvaccinated for mumps.[13]These complications include the development ofaseptic meningitisandencephalitis.[13]

The cause of breakthrough mumps is not currently completely understood. Evolution of the virus (antigenic drift) is thought to explain the majority of breakthrough cases.[13]Other theories suggest thatmemory T lymphocytesplay a role in the development of breakthrough infections.[13]

Hepatitis B[edit]

Breakthrough cases ofHepatitis Bare primarily attributed to mutations in theHepatitis B virus(HBV) that make HBV surface proteins unrecognizable to antibodies produced from theHBV vaccine.[14][15][16]Viruses with such mutations are called "vaccine escape mutants". Breakthrough infections may also be caused by delayed vaccination,immunosuppression,and maternal viral load.[15]It is possible for an individual to have breakthrough infection of HBV but be asymptomatic.[14]

COVID-19[edit]

In April 2021, scientists reported that in acohortof 417 vaccinated persons, two women had breakthrough infections as of publication and identified theirvariants' viral mutations.[17][18]In the same month, theCDCreported that in the United States, there were 5,814COVID-19breakthrough infections and 74deathsamong the more than 75 million peoplefully vaccinatedfor theCOVID-19 virus.[19][20][21][22][23][24]In July 2021, scientists reported that in an outbreak of theSARS-CoV-2 Delta variant,associated with large public gatherings, 74% of infections occurred in fully vaccinated people.[25][26]In August 2022, a study that followed up 648 vaccinated individuals found that 40% had at least one breakthrough infection. The incidence was higher in those with long term side effects of vaccination.[27]

Characteristics[edit]

Age[edit]

As a person ages, their immune system undergoes a series of changes, in a process referred to asimmunosenescence.[28]Notable among these changes is a decreased production ofnaive T cellsandnaive B cells.[29]The reduced number of naive lymphocytes (T and B cells) is attributed to the fact that thetelomeresinhematopoietic stem cells(HSCs), degenerate over time and, consequently, limit the proliferation of HSCs and production oflymphoid progenitor cells.[28][29]This is compounded by the fact that, with time, HSCs tend to favor the production ofmyeloid progenitor cellsover lymphoid progenitor cells.[29]Mature lymphocytes are also unable to proliferate indefinitely.[28]Compounded, the reduction in number of naive lymphocytes and limitations of the proliferative abilities of mature lymphocytes contribute to a limited number and variety of lymphocytes to respond to pathogens presented in a vaccine.[29]

Indeed, vaccines, including the influenza vaccine,Tdap,andpneumococcalvaccines, are less effective in adults over the age of 65.[29][30]Nevertheless, the CDC recommends that elderly adults get the flu vaccine because influenza infection is particularly dangerous in this population and vaccine provides at least a moderate level of immunity to the flu virus.[30]

Antibody interference[edit]

The presence ofmaternal antibodiesin infants limits the efficacy ofinactivated,attenuatedandsubunitvaccines.[31]Maternal antibodies can bind toepitopeson the proteins produced by the virus in the vaccination. The recognition of viral proteins by maternal antibodies neutralizes the virus.[32]Further, the maternal antibodies outcompeteB cell receptorson the infant's B cells for binding to the antigen. Thus, an infant's immune system is not highly activated and the infant produces fewer antibodies.[8][31]Even when B cells do bind to the pathogen, immune response is still frequently repressed. If B cell receptors bind to the antigen andFc receptorssimultaneously bind to the maternal antibody, the Fc receptors send a signal to B cell receptors that inhibits cell division.[32]Because the infant's immune system is not stimulated and B cell division is inhibited, few memory B cells are produced. The level of memory B-cells is not adequate to ensure an infant's lifelong resistance to the pathogen.[31][32]

In most infants, maternal antibodies disappear 12–15 months after birth, so vaccines administered outside this window are not compromised by maternal antibody interference.[8]

Longevity of memory B cells[edit]

When an individual is vaccinated against a disease, the individual's immune system is triggered andmemory B cellsstore the specific antibody response.[8]These cells remain in circulation until the pathogen infection is cleared. Because the telomeres in genes degenerate after each successive cell division, lymphocytes, including memory B cells are not capable of proliferating indefinitely.[28]Typically, the cells live for multiple decades, but there is variation in the longevity of these cells depending on the type of vaccine they were stimulated with and the vaccine dosage.[32]The reason for the differences in the longevity of memory B cells is currently unknown. However, it has been proposed that the differences in memory B cell longevity are due to the speed at which a pathogen infects the body and, accordingly, the number and type of cells involved in the immune response to the pathogen in the vaccine.[33]

Virus evolution[edit]

When a person is vaccinated, their immune system develops antibodies that recognize specific segments (epitopes) viruses or viral-induced proteins. Over time, however, viruses accumulategenetic mutationswhich can impact the 3D structure of viral proteins.[34]If these mutations occur in sites that are recognized by antibodies, the mutations block antibody binding which inhibits the immune response.[35]This phenomenon is called antigenic drift. Breakthrough infections of Hepatitis B and mumps are partially attributed to antigenic drift.[13][15]

Vaccine quality and administration[edit]

Vaccines may fail to provide immunity if the vaccine is of poor quality when administered. A vaccine loses potency if it is stored at the incorrect temperature or if it is kept after the expiration date.[36]Similarly, appropriate vaccine dosage is essential to ensuring immunity. Vaccine dosage is dependent on factors including a patient's age and weight.[36]Failure to account for these factors can lead to patients receiving an incorrect amount of vaccination. Patients that receive a lower dose than recommended of a vaccine do not have an adequate immune response to the vaccine to ensure immunity.[32]

In order for a vaccine to be effective, an individual must respond to the pathogens in a vaccine through theadaptive branchof the immune system and that response must be stored in an individual'simmunological memory.[8]It is possible for an individual to neutralize and clear a pathogen through thehumoral responsewithout activating the adaptive immune response.[8]Vaccines with weaker or fewer strains of a pathogen, as is the case when a vaccine is of poor quality when administered, may primarily elicit the humoral response, and, thus, fail to ensure future immunity.[8]

References[edit]

  1. ^CDC (2020-02-11)."COVID-19 Vaccination".Centers for Disease Control and Prevention.Retrieved2022-01-06.
  2. ^"Factsheet for health professionals".ecdc.europa.eu.Archived fromthe originalon 2017-02-24.Retrieved2017-02-24.
  3. ^"Chickenpox | Clinical Overview | Varicella | CDC".www.cdc.gov.Retrieved2017-02-24.
  4. ^"Use of Antivirals | Health Professionals | Seasonal Influenza (Flu)".CDC.gov.Retrieved2017-02-24.
  5. ^abcd"Chickenpox (Varicella)".Center for Disease Control and Prevention.1 July 2016.
  6. ^Osterholm, Michael T; Kelley, Nicholas S; Sommer, Alfred; Belongia, Edward A (2012). "Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis".The Lancet Infectious Diseases.12(1): 36–44.doi:10.1016/s1473-3099(11)70295-x.PMID22032844.
  7. ^Fine, P.; Eames, K.; Heymann, D. L. (2011-04-01).""Herd Immunity": A Rough Guide ".Clinical Infectious Diseases.52(7): 911–916.doi:10.1093/cid/cir007.ISSN1058-4838.PMID21427399.
  8. ^abcdefgOwen, Judith; Punt, Jenni; Stranford, Sharon (2013).Kuby Immunology(7th ed.). New York City, New York: W.H. Freeman and Company. pp. 576–578.ISBN978-14292-1919-8.
  9. ^abcPapaloukas, Orestis; Giannouli, Georgia; Papaevangelou, Vassiliki (2014-03-01)."Successes and challenges in varicella vaccine".Therapeutic Advances in Vaccines.2(2): 39–55.doi:10.1177/2051013613515621.ISSN2051-0136.PMC3991154.PMID24757524.
  10. ^"Pinkbook | Varicella | Epidemiology of Vaccine Preventable Diseases | CDC".www.cdc.gov.Retrieved2017-02-17.
  11. ^"Factsheet for health professionals".ecdc.europa.eu.Archived fromthe originalon 2017-02-24.Retrieved2017-02-17.
  12. ^"Mumps | Cases and Outbreaks | CDC".www.cdc.gov.Retrieved2017-02-17.
  13. ^abcdeLatner, Donald R.; Hickman, Carole J. (2015-05-07)."Remembering Mumps".PLOS Pathogens.11(5): e1004791.doi:10.1371/journal.ppat.1004791.ISSN1553-7374.PMC4423963.PMID25951183.
  14. ^abSeed, Clive R.; Jones, Ngaire T.; Pickworth, Anne M.; Graham, Wendy R. (2012-01-01)."Two cases of asymptomatic HBV" vaccine breakthrough "infection detected in blood donors screened for HBV DNA".Medical Journal of Australia.196(10): 651–652.doi:10.5694/mja11.11589.ISSN0025-729X.PMID22676882.S2CID23463146.
  15. ^abcChang, Mei-Hwei(2010). "Breakthrough HBV infection in vaccinated children in Taiwan: surveillance for HBV mutants".Antiviral Therapy.15(3 Part B): 463–469.doi:10.3851/imp1555.PMID20516566.
  16. ^Coleman, Paul F. (2017-02-17)."Detecting Hepatitis B Surface Antigen Mutants".Emerging Infectious Diseases.12(2): 198–203.doi:10.3201/eid1203.050038.ISSN1080-6040.PMC3293431.PMID16494742.
  17. ^Howard, Jacqueline."Only 2 'breakthrough' infections among hundreds of fully vaccinated people, new study finds".CNN.Retrieved11 May2021.
  18. ^Hacisuleyman, Ezgi; Hale, Caryn; Saito, Yuhki; Blachere, Nathalie E.; Bergh, Marissa; Conlon, Erin G.; Schaefer-Babajew, Dennis J.; DaSilva, Justin; Muecksch, Frauke; Gaebler, Christian; Lifton, Richard; Nussenzweig, Michel C.; Hatziioannou, Theodora; Bieniasz, Paul D.; Darnell, Robert B. (21 April 2021)."Vaccine Breakthrough Infections with SARS-CoV-2 Variants".New England Journal of Medicine.384(23): 2212–2218.doi:10.1056/NEJMoa2105000.PMC8117968.PMID33882219.
  19. ^Gilbert, Ben; Brubeck, Hilary (15 April 2021)."CDC: 5,800 COVID-19 infections, 74 deaths in the more than 75 million fully vaccinated people".Business Insider.Retrieved18 April2021.
  20. ^Krieger, Lisa M. (15 April 2021)."COVID vaccines: The mystery of" breakthrough "infections after shots - CDC reports 5,800 COVID-19 infections, 74 deaths in fully vaccinated people".The Mercury News.Retrieved18 April2021.
  21. ^Tinker, Ben; Fox, Maggie (15 April 2021)."CDC reports 5,800 COVID-19 infections, 74 deaths in fully vaccinated people".Orange County Register.Retrieved18 April2021.
  22. ^Masson, Gabrielle (15 April 2021)."5,800 COVID-19 infections detected among 77 million fully vaccinated people: CDC".Beckers Hospital Review.Retrieved18 April2021.
  23. ^May, Brandon (15 April 2021)."COVID-19 Infection After Vaccine is Rare But Possible, CDC Says".BioSpace.Retrieved18 April2021.
  24. ^Whelan, Robbie (15 April 2021)."CDC Identifies Small Group of Covid-19 Infections Among Fully Vaccinated Patients - Incidence is rare, occurring in only 0.008% of cases and in line with expectations".The Wall Street Journal.Retrieved18 April2021.
  25. ^Wadman, Meredith (4 August 2021)."What does the Delta variant have in store for the United States? We asked coronavirus experts".Science News.Retrieved2021-08-23.In the Massachusetts outbreak, fully vaccinated people accounted for 74% of nearly 469 COVID-19 cases.
  26. ^Brown, Catherine M. (2021)."Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings — Barnstable County, Massachusetts, July 2021".MMWR. Morbidity and Mortality Weekly Report.70(31): 1059–1062.doi:10.15585/mmwr.mm7031e2.ISSN0149-2195.PMC8367314.PMID34351882.S2CID236935466.
  27. ^Gabashvili IS The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups JMIR Form Res 2022;6(11):e41914 doi:10.2196/41914 PMID:36309347 PMCID:9640199
  28. ^abcdLord, Janet M. (2013-06-12)."The effect of aging of the immune system on vaccination responses".Human Vaccines & Immunotherapeutics.9(6): 1364–1367.doi:10.4161/hv.24696.ISSN2164-5515.PMC3901832.PMID23584248.
  29. ^abcdeGoronzy, Jörg J; Weyand, Cornelia M (2013)."Understanding immunosenescence to improve responses to vaccines".Nature Immunology.14(5): 428–436.doi:10.1038/ni.2588.PMC4183346.PMID23598398.
  30. ^ab"Vaccine Effectiveness - How Well Does the Flu Vaccine Work? | Seasonal Influenza (Flu) | CDC".www.cdc.gov.Retrieved2017-02-23.
  31. ^abcEdwards, Kathryn M. (2015-11-25)."Maternal antibodies and infant immune responses to vaccines".Vaccine.Advancing Maternal Immunization Programs through Research in Low and Medium Income Countries.33(47): 6469–6472.doi:10.1016/j.vaccine.2015.07.085.PMID26256526.
  32. ^abcdeSiegrist, Claire-Anne (2013). "Vaccine Immunology".Vaccines.Elsevier.ISBN9781455700905.
  33. ^"Top 20 Questions about Vaccination | History of Vaccines".www.historyofvaccines.org.Retrieved2017-02-15.
  34. ^Fleischmann, W. Robert (1996-01-01). Baron, Samuel (ed.).Medical Microbiology(4th ed.). Galveston (TX): University of Texas Medical Branch at Galveston.ISBN978-0963117212.PMID21413337.
  35. ^"Viruses and Evolution | History of Vaccines".www.historyofvaccines.org.Retrieved2017-02-11.
  36. ^abHamborsky, Jennifer; Kroger, Andrew; Wolfe, Charles (2013).Epidemiology and Prevention of Vaccine Preventable Diseases.Washington D.C.: Center for Disease Control and Prevention.

External links[edit]

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