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How Effective is Measles Vaccine?


How effective is the measles vaccine

The Centers for Disease Control (CDC) estimates that measles antibodies develop in approximately 95 percent of children vaccinated at 12 months and 98 percent of children vaccinated at 15 months or older. It is estimated that about 2-5 percent of children, who receive the vaccine at 12 months of age or younger or who only receive a single dose of MMR, fail to be protected. A second dose of MMR is thought to stimulate a protective immune response in about 99 percent of vaccine recipients.1

From 1963, when the measles vaccine was first introduced in the United States, until December of 1989, public health officials recommended that all children receive a single dose of measles vaccine beginning at 12 months of age.2

During this time, however, measles cases and outbreaks occurred among vaccinated children. In 1973, Dr. Stanley Plotkin warned that vaccinated children could still get measles and that “a history of previous vaccination cannot be assumed to exclude measles as the cause of an exanthum rash, whether typical or atypical.” He said that, “about 5 percent of vacinees do not respond and presumably remain susceptible,” which he described as “primary vaccine failures.” 3

Dr. Plotkin also stated that there was evidence that some previously vaccinated children exposed to wild type measles could “develop modified illness and a secondary type of antibody response,” which he described as “secondary vaccine failures.”4

By 1982, researchers had discovered that infants vaccinated in the first year of life were not protected from measles, even after repeated vaccine doses.5

From 1985 to 1988, there were between 55 and 110 measles outbreaks every year in the U.S., primarily in highly vaccinated school-aged populations.6 Measles swept through a middle school in Texas, where 99 percent of the students were vaccinated, and in a Massachusetts high school with a 98 percent vaccination rate.7 8

In 1989, measles cases exploded in North and Central America, including in the U.S. and were associated with unusually high morbidity and mortality. CDC officials did not offer an explanation for the increases but insisted that “measles vaccines appear to be as effective today as in the past.” 9 They did, however, state that “analysis of contemporary strains of measles virus suggest that circulating viruses may have changed somewhat from past strains.” 10

In 1998, CDC officials confirmed that the 1989-1990 measles outbreak, which caused a higher number of hospitalizations and deaths, was associated with circulation of Group 2 measles viruses, particularly D3, that were “genetically distinct from vaccine strains.” 11 12

More than 45,000 measles cases and over 100 deaths were reported in the U.S. during 1989 and 1990. Numerous outbreaks were reported among vaccinated school children but a large number of cases also occurred in babies less than 15 months old and in unvaccinated toddlers, as well as in college students. Approximately 80 percent of affected school children were found to be appropriately vaccinated.13

In December of 1989, the CDC recommended that children should receive their first dose of MMR vaccine at 15 months and all children should get a booster dose before entering kindergarten. “When fully implemented,” CDC officials stated, “this schedule should lead to the elimination of measles among school aged children and college students.” 14 They also reported that “Although the titers of vaccine-induced antibodies are lower than those following natural disease, both serologic and epidemiologic evidence indicate that vaccine-induced protection appears to be long lasting in most individuals.” 15

Published medical research, however, indicates that vaccine failure due to waning immunity can occur, despite multiple doses of measles vaccine.16 17 18  Measles vaccine acquired immunity is reported to wane in at least 5 percent of cases, within 10 to 15 years after vaccination.19 20 21  Moreover, exposure to natural measles may be necessary for the maintenance of protective antibodies in vaccinated persons.22 

The Vaccine Research Group at Minnesota’s Mayo Clinic reports that up to 10 percent of persons who receive 2 doses of MMR vaccine “fail to develop protective humoral immunity and those antibody levels wane over time, which can result in infection.”23 Further, they admit that “While the current vaccine used in the USA and many other countries is safe and effective, paradoxically in the unique case of measles, it appears to insufficiently induce herd immunity in the population.”24

Mayo Clinic researchers have also found that individuals respond differently to vaccination and each individual’s genes play a role in controlling measles vaccine-induced immune responses. They report that scientists still do not completely understand “how the immune response is generated” or “how host genetic and epigenetic variations change and impact vaccine immune responses,” or “how pathogens interact with the immune system.” 25 They also state that The importance of cellular immunity to vaccine-induced protection is not completely understood.”  Some children with no detectible measles antibodies may still be protected against measles, which supports the “involvement of cellular immunity.” 26

Further, they admit that scientists do not currently have “a detailed understanding of the pathogenesis of the measles virus” or of vaccine-induced innate and adaptive (humoral) immunity and that better correlates of protection “that go beyond measuring antibody titers” are needed. There is not enough information about what drives a vaccine response, a vaccine non-response, adverse events following vaccination and the many complex interactions between immune function-related components known at this time.27

Genetic ancestry may also play a significant role in measles vaccine responses. One cohort study found that Caucasians and most Hispanics, ethnic groups which represent nearly 80 percent of the U.S. population, showed significantly lower humoral and cellular responses to MMR vaccination than African Americans.28

Scientists are also questioning the MMR vaccine’s ability to completely protect against the currently circulating measles strains. In 2017, microbiologists from India reported that “The measles virus (MeV) is serologically monotypic but genotyping confirms eight clades (A-H). The clades are further subdivided into 23 genotypes….Although sera from vaccinated individuals neutralize all the clades, the efficacy varies from clade to clade. It may be said that the level of protection offered by this vaccine varies from genotype to genotype.” 29

Further, they stated that “The present vaccine does not offer complete protection assurance and the limitations are evident nowNewer strains show epitopes that are not shared by vaccine strains. Variations in the efficacy of neutralization in the vaccinated individuals against wild MeV has been reported.” 30

In the past 2 decades, waning immunity resulting in both asymptomatic and modified clinical illness has been documented in the medical literature.

In 1998, CDC officials acknowledged that:

“Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.”31

German virologists confirmed the results and reported that:

 “…measles virus (MV) could circulate in seropositive fully protected populations. Among individuals fully protected against disease, those prone to asymptomatic secondary immune response are the most likely to support subclinical MV transmission.” 

In 1999, European researchers found that “…a substantial proportion of individuals who respond to measles vaccine display an antibody boost accompanied by mild or no symptoms on exposure to wild virus” and in highly vaccinated populations “neutralizing antibodies are decaying significantly in absence of circulating virus.” They estimated “the mean duration of vaccine induced protection in absence of re-exposure to be 25 years,” warning that, “there is a need to establish the intensity and duration of infectiousness in vaccinated individuals.”32

In 2002, Japanese researchers reported that “measles virus can infect previously immune individuals,” both those who are naturally immune and those who have been vaccinated, and that the reinfection can produce “a wide range of illnesses: typical measles, mild modified measles and asymptomatic infection.” Researchers concluded that, “…the number of cases of measles among previously immunized individuals has increased, probably caused by waning of vaccine-induced immunity” and suggested that “…asymptomatic measles infections occur even in the adult population with unexpectedly high frequency and this supports the preservation of measles immunity.” 33

The number of vaccinated people infected with measles and who show few or no symptoms but transmit measles to others is also unknown as vaccinated individuals are not routinely surveyed to determine whether they are experiencing asymptomatic or atypical measles and transmitting it to other. 34 35 

In June 2018, Japanese researchers reporting on an outbreak of measles in Japan between March and May 2018, concluded that “… the vaccinated population may play a role in the transmission dynamics of measles – probably due to secondary vaccination failure (waning of vaccine-induced immunity to non-protective levels).” 36

In May 2019, Australian scientists reported evidence of “waning measles immunity among vaccinated individuals” that is “associated with secondary vaccine failure and modified clinical illness” with “transmission potential.”37

This finding confirmed the scientific evidence from Germany in April 2019 which reported:

“Although measles cases have gradually declined globally since the 1980s together with an increase in vaccination coverage, there has been a resurgence of measles in the European Union and European Economic Area starting in 2017 with adults aged over 20 years comprising more than a third of all cases.” 38

“The impact of waning immunity to measles will likely become more apparent over the coming years and may increase in the future, as the vaccinated population (with hardly any exposure to measles) will grow older and the time since vaccination increases. It is worth noting that the median age of measles cases has been increasing over the past 15 years in Berlin and the extent of waning immunity may increase further. Vaccinated cases have a lower viraemia and have rarely been observed to contribute to transmission. However, with the vaccinated population turning older and titres possibly decreasing further, this observation has to be re-evaluated.”39

In the past decade, outbreaks of measles in highly vaccinated populations have been documented in medical literature.

In 2011, a fully vaccinated person transmitted measles to 4 contacts, of which 2 contacts had documentation of receiving 2 prior MMR doses and 2 had confirmed blood antibody results considered protective against measles.40

In 2014, an outbreak of measles occurred among vaccinated health care workers in the Netherlands. Of the 8 confirmed cases, 6 had received 2 measles vaccines, 1 had received a single dose, and 1 worker was unvaccinated. Study authors concluded that among the 106 potentially exposed health care workers, the effectiveness of 2 doses of measles vaccine was approximately 52 percent.41

In 2017, an outbreak of measles occurred among young soldiers in Israel. The primary patient involved in the outbreak had documentation of having received 3 doses of measles vaccine and the additional 8 cases of measles were found to have occurred in persons who reported having, or provided documentation of having, at least 2 doses of a measles containing vaccine.42

A 2016 published study conducted by the CDC, FDA, and Johns Hopkins Bloomberg School of Public Health found that the use of a third dose of MMR vaccine in an attempt to boost antibodies in persons with low measles antibodies was not effective.43

Merck’s MMRII product information insert states that if infants born to mothers who have experienced natural measles infection are vaccinated at less than one year of age, they may not develop long lasting vaccine acquired antibodies. Natural maternal measles antibodies interfere with the vaccine’s ability to produce antibodies, which may result in vaccine failure.44

Additional research on maternal measles antibodies concluded that infants born to mothers who were vaccinated against measles have lower levels of maternal antibodies and lost them sooner in comparison to infants born to naturally immune mothers. 45 46  As a result, most infants younger than 12 months who are born to measles vaccinated mothers “lack both passive and active immunity, leaving them unprotected and in the highest-risk group for life-threatening complications.” 47

IMPORTANT NOTE: NVIC encourages you to become fully informed about Measles and the Measles vaccine by reading all sections in the Table of Contents , which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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References

1 CDC Measles – Measles Vaccine Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.

2 CDC ACIP recommendations 1969 : collected recommendations of the Public Health Service Advisory Committee on Immunization Practices MMWR 18(43): 1-31

3 Plotkin SA. Failures of protection by measles vaccineJ Pediatr 1973; 82(5): 908-911.

4 Ibid

5 Linnemann CC, Dine MS et al. Measles Immunity After Revaccination: Results in Children Vaccinated Before 10 Months of AgePediatrics 1982; 69(3).

6 Atkinson WL, Orenstein WA, Krugman S. The resurgence of measles in the United States, 1989-1990Annu Rev Med 1992; 43: 451-463.

7 Gustafson TL, Lievens AW et al. Measles outbreak in a fully immunized secondary-school population. N Engl J Med 1987; 316(13): 771-774.

8 Nkowane BM, Bart SW et al. Measles outbreak in a vaccinated school population: epidemiology, chains of transmission and the role of vaccine failuresAm J Public Health 1987; 77(4): 434-438.

9 Atkinson WL, Orenstein WA, Krugman S. The resurgence of measles in the United States, 1989-1990Annu Rev Med 1992; 43: 451-463.

10 Ibid

11 Bellini WJ, Rota PA. Genetic Diversity of Wild-Type Measles Viruses: Implications for Global Measles Elimination ProgramsEmerg Infect Dis 1998; 4(1).

12 Rota PA, Bellini WJ. Update on the Global Distribution of Genotypes of Wild Type Measles Viruses. J Infect Dis 2003; 187(Suppl 1) S270-S276.

13 Wood DL, Brunell PA. Measles control in the United States: problems of the past and challenges for the futureClin Microbiol Rev 1995; 8(2): 260-267.

14 CDC Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP) MMWR Dec 29, 1989; 38(S-9);1-18

15 Ibid

16 Kang HJ, Han YW, Kim SJ et al. An increasing, potentially measles-susceptible population over time after vaccination in Korea. Vaccine. 2017 Jul 24; 35(33):4126-4132.

17 Hahné SJ, Nic Lochlainn LM, van Burgel ND et al. Measles Outbreak Among Previously Immunized Healthcare Workers, the Netherlands, 2014. J Infect Dis. 2016 Dec 15; 214(12):1980-1986.

18 Rosen JB, Rota JS, Hickman CJ et al. Outbreak of measles among persons with prior evidence of immunity, New York City, 2011. Clin Infect Dis. 2014 May; 58(9):1205-10

19 Sabella C. Measles: Not just a childhood rash Cleve Clin J Med 2010 Mar. 77(3):207-213

20 Markowitz LE, Preblud SR, Fine PE, Orenstein WA. Duration of Live Measles Vaccine-Induced Immunity. Pediatr Infect Dis J. 1990; 9:101-110.

21 Anders JF, Jacobsen RM, Poland GA, et al. Secondary Failure Rates of Measles Vaccines: a Meta-analysis of Published Studies. Pediatr Infect Dis J. 1996 Jan;15(1):62-6.

22 Aaby P, Cisse B, Simondon F, et al.  Waning of Vaccine-Induced Immunity: Is It a Problem in Africa? Am J Epidemiol 1999 Feb. 15;149(4); 304-305

23 Haralambieva IH, Ovsyannikova IG et al. The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approachesExpert Rev Vaccines 2013; 12(1): 57-70.

24 Ibid

25 Haralambieva IH, Ovsyannikova IG et al. The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approachesExpert Rev Vaccines 2013; 12(1): 57-70.

26 Haralambieva IH, Kennedy RB et al. Variability in Humoral Immunity to Measles Vaccine: New DevelopmentsTrends Mol Med 2015; 21(12): 789-801.

27 Ibid

28 Voight EA, Ovsyannikova IG et al. Genetically defined race, but not sex, is associated with higher humoral and cellular immune responses to measles vaccination. Vaccine 2016; 34(41): 4913-4919.

29 Kulkarni RD, Ajantha GS et al. Global eradication of measles: Are we poised? Indian J Med Microbiol 2017; 35(1): 10-16.

30 Ibid

31 Helfand RF, Kim DK et al. Nonclassic measles infections in an immune population exposed to measles during a college bus tripJ Med Virol 1998; 58(4): 337-341.

32 Mossong J, Nokes DJ et al. Modeling the impact of subclinical measles transmission in vaccinated populations with waning immunityAm J Epidemiol 1999; 1:150(11): 1238-1249.

33 Sonoda S, Kitahara M, Nakayama T. Detection of measles virus genome in bone-marrow aspirates from adults. J Gen Virol 2002; 83: 2485-2488.

34 Whittle HC, Aaby P, Samb B et al. Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa. Lancet. 1999 Jan 9; 353(9147):98-102.

35 Mossong J, Muller CP. Modelling Measles Re-Emergence as a Result of Waning of Immunity in Vaccinated Populations. Vaccine. Nov. 7, 2003.  21 (31); 4597-4603.

36 Mizumoto K, Kobayashi, T, Chowell G Transmission potential of modified measles during an outbreak, Japan, March‒May 2018 Euro Surveill. 2018 Jun 14; 23(24): 1800239.

37 Gibney KB, Attwood LO et al. Emergence of attenuated measles illness among IgG positive/IgM negative measles cases, Victoria, Australia 2008-2017Clin Infect Dis May 6, 2019.

38 Bitzegeio J, Majowicz S et al. Estimating age-specific vaccine effectiveness using data from a large measles outbreak in Berlin, Germany, 2014-2015: evidence for waning immunity. Eurosurveillance 2019; 24(17). 

39 Ibid

40 Rosen JB, Rota JS, Hickman CJ et al. Outbreak of measles among persons with prior evidence of immunity, New York City, 2011. Clin Infect Dis. 2014 May; 58(9):1205-10.

41 Hahné SJ, Nic Lochlainn LM, van Burgel ND et al. Measles Outbreak Among Previously Immunized Healthcare Workers, the Netherlands, 2014. J Infect Dis. 2016 Dec 15;214(12):1980-1986

42 CDC Measles Outbreak in a Highly Vaccinated Population — Israel, July–August 2017. MMWR. Oct. 26, 2018; 67(42);1186–1188

43 Fiebelkorn AP, Coleman LA, Belongia EA et al. Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults. J Infect Dis. 2016 Apr 1;213(7):1115-23

44 FDA Measles, Mumps and Rubella Virus Vaccine, Live  May 16, 2017

45 Waaijenborg S, Hahné SJ, Mollema L et al. Waning of maternal antibodies against measles, mumps, rubella, and varicella in communities with contrasting vaccination coverage. J Infect Dis. 2013 Jul;208(1):10-6

46 Zhao H, Lu P-S, Hu Yali, et al. Low Titers of Measles Antibody in Mothers Whose Infants Suffered from Measles before Eligible Age for Measles Vaccination. Virology 2010, 7:87.

47 Gans HA, Arvin AM, Galinus J et al. Deficiency of the Humoral Immune Response to Measles Vaccine in Infants Immunized at Age 6 MonthsJAMA 1998; 280(6): 527-532.


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