History of Measles Vaccine

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From the National Vaccine Information Center (NVIC)

The first two measles vaccines were initially licensed for use in the United States in 1963 and both contain the Edmonston B measles strain isolated by John Enders in 1954. Rubeovax, a live attenuated vaccine, was manufactured by Merck while Pfizer-Vax Measles-K, an inactivated (killed) virus vaccine, was manufactured by Pfizer.1

At the time of vaccine approval, a single dose of the live attenuated Rubeovax was reported to be 95 percent effective at preventing measles, and protection from measles infection lasted at least three years and eight months. However, 30 to 40 percent of children who received Rubeovax experienced fever of 103 degrees or higher beginning on or around the sixth day following vaccination, lasting between 2 to 5 days. 30 to 60 percent of individuals who received Rubeovax also developed a “modified measles rash”.2 Due to the high number of side effects, public health and Merck officials recommended that Rubeovax be administered in conjunction with measles immune globulin, as co-administration significantly reduced vaccine reactions.3 4

Pfizer-Vax Measles–K, Pfizer’s inactivated measles virus vaccine given in a series of three vaccines at one month intervals, was much less reactive but the vaccine offered limited effectiveness against the disease. In fact, the majority of children who received the vaccine had no detectable levels of measles antibodies when tested one year later.5

By 1965, doctors were reporting of a new and abnormal measles-like illness (atypical measles) in children previously vaccinated with inactivated measles virus vaccine upon exposure to measles. Symptoms of atypical measles included rash, swelling, fever, pneumonia, and pleural effusion.6 Pfizer’s inactivated measles vaccine was removed from the market in 1968.7

Prior to 1963, Enders permitted other vaccine researcher to work with the Edmonston measles strain in order to develop less reactive measles vaccines.8 

As a result, several additional live attenuated measles vaccines using the Edmonston B measles strain were also approved for use in 1963. These vaccines included M-Vac, manufactured by Lederle Pharmaceuticals, and various generic measles vaccines manufactured by pharmaceutical companies which included Parke Davis, Eli Lilly, and more. In addition to its inactivated measles vaccine, Pfizer also introduced Pfizer-Vax Measles-L, a live attenuated measles vaccine, in 1965.9

By 1975, however, all previously FDA approved measles vaccines had been discontinued and replaced with two newer and more attenuated virus vaccines- Lirugen, manufactured by Pitman Moore-Dow, and Attenuvax, manufactured by Merck. Lirugen and Attenuvax were developed for use in the mid-1960s in response to the significant number of reported side effects from earlier live vaccines 10

Lirugen was developed from the Schwarz measles strain, a strain created by further attenuation of the Edmonston A measles strain. Lirugen was discontinued in the U.S. in 1976 but vaccines derived from the Schwarz measles strain remain in use outside the U.S.11 12 13

Attenuvax live attenuated measles virus vaccine was developed from the Moraten measles strain, a strain created by further attenuation of the Edmonston B measles strain. Attenuvax was initially approved for use in the U.S. in 196814 and is currently found in both Merck’s Measles-Mumps-Rubella combination vaccine, MMRII,15 and in its Measles-Mumps-Rubella-Varicella vaccine, ProQuad (MMR-V).16

In March 1967, public health officials announced that measles could be eradicated from the United States within a few months by use of the newly approved measles vaccines.17

CDC officials published a paper in the medical literature describing measles virus as one that “has maintained a remarkably stable ecological relationship with man” and that measles “complications are infrequent.” 18 They also reported that “with adequate medical care, fatality is rare” and that “immunity following recovery is solid and lifelong in duration.” 19 Further, they stated that a 55 percent herd immunity threshold or more may be needed to prevent measles epidemics that cycle in communities every two to three years but that, “there is no reason to question that…the immune threshold is considerably less than 100 percent.” 20

However, mass vaccination of infants beginning at approximately one year of age and the push for all children entering school to receive a dose of measles vaccine did not result in measles eradication and outbreaks continued to occur in highly vaccinated populations.21 22

By 1971, public health officials noted that measles outbreaks were on the rise and blamed the increasing number of measles cases on unvaccinated children and the lack of legislation in many states to require measles vaccination as a condition of school entry. Public health officials, however, acknowledged that vaccine failure played a role in outbreaks and blamed factors such as vaccination prior to 9 months of age, the use of measles gamma globulin, and improper vaccine handling and storage in addition to the vaccine’s 3 to 5 percent failure rate. The goal of measles eradication in the United States was no longer considered quickly achievable and researchers questioned whether it could be accomplished at all.23

Measles outbreaks continued to occur throughout the 1970’s and 1980’s, impacting mainly pre-school and school aged children, many of whom had been appropriately vaccinated.24 Despite these continued outbreaks, in 1979, public health officials launched an effort to eliminate measles from the United States through vaccination, by October 1st, 1982.25 In 1982, there were a record low 1,697 reported measles cases in the United States26 and while public health officials admitted to failure, they publicly stated eradication to be “right around the corner”.27

Measles cases decreased again in 1983, but in 1984, a thousand more cases were reported to the CDC.28 In 1985, nearly 300 additional cases of measles had been reported than the previous year, and of the 2,813 reported measles cases, 44 percent had occurred in appropriately vaccinated children.29

Another measles resurgence occurred in 1989, and by the end of that year, 18,193 cases had been reported to the CDC,30 with over 40 percent of infections occurring in fully vaccinated individuals.31 The CDC blamed the outbreaks on both the failure of implementing vaccine programs, particularly those aimed at vaccinating preschool children, as well as on vaccine failure. While blaming the measles outbreaks on vaccine failure, the CDC continued to report a 95 percent measles vaccine effectiveness rate, all while denying that vaccine induced immunity was waning.32

In 1989, the CDC’s Advisory Committee on Immunization Practices (ACIP) updated its measles vaccine recommendations and recommended that all children receive two doses of MMR vaccine prior to school entry, with the first dose at 15 months, and the second dose at 4 to 6 years, prior to school entry.33

Also, in 1989, the CDC sponsored a study of two different measles vaccines on minority children living in the Los Angeles area. One of the measles vaccines used in the study was an unlicensed, experimental vaccine but the parents of children participating in the study were not made aware of this detail.34

The experimental vaccine that was used was a high dose measles vaccine aimed at overwhelming the natural maternal antibodies which protect infants from infection during the first year of life. The presence of maternal antibodies at time of vaccination can lead to vaccine failure and the risk of measles infection later in life. While the vaccine had been in use outside of the country, by 1990, a high number of deaths in female children 6 months to 3 years after vaccination had been reported.35

The study was halted in 1991 but the public was not informed of the study details until 1996. The CDC reported that no injuries or deaths occurred as a result of the use of the unlicensed, experimental vaccine; however, one child participant from the study died of a bacterial infection, which the CDC maintains to be unrelated to vaccination.36

In 1998, concerns over safety of the combination measles-mumps-rubella (MMR) vaccine surfaced following the publication of a case study involving 12 previously healthy children who developed severe gastrointestinal disorders after receiving the vaccine.37 Eight of the 12 children involved in the study also developed autism, with parents and personal physicians reporting symptom onset nearly immediately following MMR vaccine administration. The 13 physicians involved in the study also reported that they had investigated over 40 similar cases to the ones described in the published study. Study authors did not claim that the MMR vaccine was responsible for the gastrointestinal health problems but recommended for further research into the potential association.38

Following publication, scientists involved in the study, including lead author Dr. Andrew Wakefield, a well-respected gastroenterologist practicing at the United Kingdom’s Royal Free hospital, became the target of public health officials and vaccine policymakers.39

In late 2000, Wakefield and two contributing researchers, Dr. John Walker-Smith and Dr. Simon Murch, were brought up on charges of scientific misconduct by the UK’s General Medical Council (GMC) related to the published case study. Wakefield and Walker-Smith were found guilty in May 2010 and both physicians lost their medical licenses as a result.40

Walker-Smith, however, appealed the verdict and in 2012, a U.K. high court reversed the decision. The presiding judge in the appeal case criticized the GMC’s disciplinary panel’s decision, and stated that “It would be a misfortune if this were to happen again.”41 Findings from the case study have been replicated;42 43 however, Wakefield continues to be a frequent target of the press and medical community.44 45

In August 2014, William Thompson, a senior scientist at the CDC, came forward with allegations that CDC researchers purposely omitted data in 2004 in a study examining the MMR vaccine and autism among African American boys.46 According to Thompson, researchers involved in the 2004 study found a link between the MMR vaccine and autism in this population but chose to destroy the data.47

After Thompson’s disclosure, Florida Senator Bill Posey called for an investigation of the CDC scientists involved in the study to determine whether fraud had been committed in an attempt to cover up a link between the MMR vaccine and autism.48

Thompson’s allegations became the subject of Vaxxed: From Cover-Up to Catastrophe, a documentary first scheduled for debut at New York City’s Tribeca Film Festival in April 2016. The film, however, was dropped from the festival’s lineup after pressure and attacks by the media and others.49 As a result, the film’s first showing occurred at Manhattan’s Angelika Film Center on April 1, 2016.50 Government officials have yet to investigate the allegations brought forward by Thompson against his fellow CDC scientists.

In early January 2015, the CDC began investigating and outbreak of measles linked to California’s Disneyland theme park resort. In a statement released on January 23, 2015, the CDC announced that 51 confirmed cases of measles had been linked to the outbreak and encouraged MMR vaccination.51 Hundreds of measles outbreak news stories followed in the media, with many articles vilified parents of unvaccinated children while blaming them for the outbreak.52

The Disneyland outbreak prompted several state legislators to introduce vaccine legislation aimed at eliminating or severely restricting religious and conscientious/philosophical vaccine exemptions. Vaccine choice advocates were highly successful in defeating many restrictive bills; however, California lost its personal belief exemption and Vermont lost its philosophical exemption but retained its religious vaccine exemption.53

In 2015, only 188 cases of measles were reported in the U.S.,54 a 72 percent decrease from the previous year.55 Of these cases, 147 were linked to the outbreak in California.56

Measles increased again in January 2019, with outbreaks linked to travelers returning from countries such as the Philippines, Israel, and the Ukraine, where large outbreaks were ongoing. By mid-January, the World Health Organization (WHO) announced “vaccine hesitancy” to be one of the top ten global health threats 57 and the U.S. government and media responded by launching an unprecedented response.58

In Rockland County, New York, instead of quarantining people infected with measles, government officials threatened parents of healthy unvaccinated children with fines and imprisonment if their children appeared in public spaces – the first time ever in American history.59 60 61 Unvaccinated children and adults living, working or visiting in neighborhoods with certain zip codes in Brooklyn were threatened with steep fines if found in contact with someone with measles.62

State legislatures, including Arizona, New York, Connecticut, New Jersey, Minnesota, Iowa, Alabama, Missouri, Maine, Massachusetts, Ohio, Oregon, Pennsylvania, Washington, and Wisconsin, were quick to introduce bills aimed at eliminating religious and conscientious/philosophical vaccine exemptions for school entry.63 64 65 66 67 68 69 70 71 72 73 74 75 76 77

California introduced and amended a bill to severely restrict its medical exemption, by punishing doctors for writing exemptions and investigating schools with vaccine exemption rates lower than 95 percent.78

Washington State passed a bill eliminating the philosophical exemption for the MMR vaccine,79 and Maine’s legislature voted to remove both its religious and philosophical exemption for all vaccines.80

On June 13, 2019, the New York State legislature repealed its religious exemption to vaccination in one day, without permitting any public hearings.81

The CDC’s Advisory Committee on Immunization Practices (ACIP) currently recommends that all children receive 2 doses of MMR vaccine. The first dose is recommended at 12-15 months and the second dose at 4 to 6 years, prior to school entry.82

Measles vaccination rates remain high in the U.S. In 2017, the CDC reported that 94 percent of children entering kindergarten had received two doses of MMR vaccine.83 For the 2018-2019 school year, 94.7 percent of children in kindergarten had received the two recommended doses of MMR vaccine.84

Further, in 2020, 92.4 percent of adolescents 13 to 17 years were reported to have received the two recommended MMR vaccine doses.85

In June 2022, the FDA approved PRIORIX, a live attenuated measles, mumps, and rubella vaccine, manufactured by GlaxoSmithKline.86 PRIORIX was initially licensed in Germany in 1997 and according to the CDC, the vaccine has been in use globally in nearly 100 countries.87 On June 23, 2022, the CDC’s ACIP voted to approve use of PRIORIX as an option for the MMR vaccine according to the current MMR recommendations and off-label uses.88

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.

 

 


References:

[1] Hendriks J, Blume S. Measles Vaccination Before the Measles-Mumps-Rubella Vaccine Am J Public Health Aug 2013;103(8):1393-401.

[2] Terry LL. The Status of Measles Vaccines – A Technical Report J Natl Med Assoc. Sep 1963; 55(5): 453–455.

[3] Terry LL. The Status of Measles Vaccines – A Technical Report J Natl Med Assoc. Sept. 1963; 55(5): 453–455.

[4] Galambos L, Sewell JE Networks of Innovation: Vaccine Development at Merck, Sharp & Dohme, and Mulford, 1895-1995. Cambridge University Press, 1997.

[5] Terry LL The Status of Measles Vaccines – A Technical Report J Natl Med Assoc. Sept. 1963; 55(5): 453–455.

[6] Rauh LW. Schmidt R. Measles immunization with killed virus vaccine. Serum antibody titers and experience with exposure to measles epidemic. 1965. Bull World Health Organ. 2000; 78(2): 226–231.

[7] U.S. Centers for Disease Control and Prevention. Selected Discontinued U.S. Vaccines Epidemiology and Prevention of Vaccine-Preventable Diseases, 13th Edition.

[8] Hendriks J, Blume S. Measles Vaccination Before the Measles-Mumps-Rubella Vaccine Am J Public Health. Aug 2013;103(8):1393-401.

[9] Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118.

[10] Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118.

[11] U.S. Centers for Disease Control and Prevention. Selected Discontinued U.S. Vaccines Epidemiology and Prevention of Vaccine-Preventable Diseases, (The Pink Book) 13th Edition.

[12] Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118.

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[14] Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Events Associated with Childhood Vaccines (Evidence Bearing on Causality). Washington, DC: The National Academies Press. 1994 Chap. 6. P. 118.

[15] Merck, Sharp & Dohme Corp. Package Insert – Measles, Mumps and Rubella Virus Vaccine, Live. U.S. Food and Drug Administration Dec. 14, 2020.

[16] Merck Sharpe & Dohme Corp. Package Insert – Refrigerator-Stable Formulation – ProQuad. U.S. Food and Drug Administration Apr. 16, 2021.

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[23] Conrad JL, Wallace R, Witte JJ. The epidemiologic rationale for the failure to eradicate measles in the United States. Am J Public Health. November 1971; 61(11): 2304–2310.

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[25] Hinman AR, Brandling-Bennett AD, Nieburg PI. The opportunity and obligation to eliminate measles from the United States. JAMA Sep 14, 1979; 242(11):1157-62.

[26] U.S. Centers for Disease Control and Prevention. Current Trends Measles — United States, 1982 MMWR Feb. 4, 1983; 32(4):49-5.

[27] Associated Press U.S. Cases of Measles Are Almost Eradicated. The New York Times Oct. 3, 1982.

[28] U.S. Centers for Disease Control and Prevention. Current Trends Measles — North America, 1984. MMWR Jun. 21, 1985; 34(24):366-70.

[29] U.S. Centers for Disease Control and Prevention. Measles — United States, 1985. MMWR Jun. 6, 1986; 35(22):366-70.

[30] U.S. Centers for Disease Control and Prevention. Summary of notifiable diseases, United States, 1989. MMWR Oct. 5, 1990; 42 (53):1-67.

[31] U.S. Centers for Disease Control and Prevention. Current Trends Measles — United States, 1989 and First 20 Weeks 1990. MMWR Jun 1, 1990; 39(21):353-355,361-363.

[32] U.S. Centers for Disease Control and Prevention. Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Dec 29,1989; 38(S-9):1-18.

[33] U.S. Centers for Disease Control and Prevention. Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Dec 29,1989; 38(S-9):1-18.

[34] Cimons M. CDC Says It Erred in Measles Study. Los Angeles Times Jun. 17, 1996.

[35] Fisher BL. Measles Vaccine Experiments on Minority Children Turn Deadly. NVIC Commentary June 1996. Vol 2 No 2. Online.

[36] Fisher BL. Measles Vaccine Experiments on Minority Children Turn Deadly. NVIC Commentary June 1996. Vol 2 No 2. Online.

[37] Wakefield AJ, Murch SH, Anthony A et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet Feb 28, 1998;351(9103):637-41. (Retracted)

[38] National Vaccine Information Center. Research into Vaccines, Autism and Intestinal Disorders Published in the Lancet. Mar. 3, 1998.

[39] National Vaccine Information Center. Research into Vaccines, Autism and Intestinal Disorders Published in the Lancet. Mar. 3, 1998.

[40] Boseley S. Andrew Wakefield struck off register by General Medical Council. The Guardian May. 24, 2010.

[41] Aston J. MMR DOCTOR JOHN WALKER-SMITH WINS HIGH COURT APPEAL. The Independent Mar. 7, 2012.

[42] Beck S. Scientists fear MMR link to autism. The Daily Mail May 28, 2006.

[43] Wake Forest Baptist Medical Center. Wake Forest Researcher Warns Against Making Connection Between Presence of Measles Virus and Autism News Release Jun. 1, 2006.

[44] Buncombe A. Andrew Wakefield: How a disgraced UK doctor has remade himself in anti-vaxxer Trump’s America. The Independent May 4, 2018.

[45] Blanchard S. Discredited doctor Andrew Wakefield who falsely claimed MMR jabs lead to autism is handed ‘bad science’ award – 20 years after his ‘fatally flawed’ report was published. The Daily Mail Oct. 16, 2018.

[46] Attkisson S. (Audio) CDC Addresses Allegations on Vaccine-Autism Link Omission. SharylAttkisson.com Aug. 29, 2014.

[47] Posey B (Transcript). Congressman Wants CDC Investigated for Tampering With MMR Study. The Vaccine Reaction Aug. 1, 2015.

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[49] Cáceres M. When the Media Thinks and Concludes for the People. The Vaccine Reaction Mar. 29, 2016.

[50] Ryzik M. Anti-Vaccine Film, Pulled From Tribeca Film Festival, Draws Crowd at Showing. The New York Times Apr. 1, 2016.

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[53] National Vaccine Information Center. State Vaccine Legislation in America 2015-2017. Oct 25, 2017.

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[57] World Health Organization (WHO). Ten Threats to Global Health in 2019. 2019.

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[59] Tampone K. Rockland County’s Ban on Unvaccinated Minors from Public Carries Fine, JailPost Standard Mar. 27, 2019.

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[65] Altimari D. Lawmakers hear testimony on proposal to end religious exemption to vaccination. Hartford Courant May 13, 2019.

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[67] Murphy E. Hundreds Rally To Oppose Bill Limiting Vaccine Exemptions. WCCO 4 CBS Minnesota Feb. 25. 2019.

[68] Lynch JQ. Iowa lawmakers propose competing changes to vaccination exemptions. Quad-City Times Feb. 18, 2019.

[69] Gore L. Religious exemption to vaccines would be eliminated under new Alabama bill. Al.com May 9, 2019.

[70] Baiter K. Missouri faces vaccination hesitancy amid measles case. AP News Apr. 5, 2019.

[71] Gov. Mills kicks off flip-flop season killing religious vaccine exemption, names CDC head with troubles in Illinois. Maine Examiner May 26, 2019.

[72] Lannan K. Mass. Sees 2nd Measles Case This Year. Now There’s A Bill To Remove Religious Exemption For Vaccines. 90.9 wbur Jun. 3, 2019.

[73] Borchardt J. Not vaccinated? A new Ohio bill could prevent you from being fired for refusing immunizations. Cincinnati Enquirer June 29, 2019.

[74] VanderHart D. Tougher Vaccine Laws Pass Oregon House, Head To Senate. OPB.org May 7, 2019.

[75] Snyder M. Pennsylvania bill would end religious, philosophical exemptions from vaccines. ABC News 27 Mar. 29, 2019.

[76] Sun LH, Millares Young K. Washington measles outbreak draws crowd to hearing on vaccine law. The Washington Post Feb. 8, 2019.

[77] Associated Press. Wisconsin governor backs pro-vaccination bill. NBC 26 Apr. 30, 2019.

[78] Associated Press. California Bill to Tighten Vaccine Exemptions Amended to Sharpen Focus on Bad Doctors. KTLA5 June 18, 2019.

[79] Wamsley L. Washington State Senate Passes Bill Removing Exemption For Measles Vaccine. NPR.com Apr. 18, 2019.

[80] Gov. Mills kicks off flip-flop season killing religious vaccine exemption, names CDC head with troubles in Illinois. Maine Examiner May 26, 2019.

[81] National Vaccine Information Center. New York Bill Removing Religious Vaccine Exemption Turned Into Law on One Day with No Public Hearings. The Vaccine Reaction June 14, 2019.

[82] McLean HQ, Fiebelkorn AP. Temte JL. et al. Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013: Summary Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Jun. 14, 2013; 62(RR04):1-34.

[83] Seither R, Calhoun K, Street EJ, et al. Vaccination Coverage for Selected Vaccines, Exemption Rates, and Provisional Enrollment Among Children in Kindergarten — United States, 2016–17 School Year. MMWR Oct. 13, 2017; 66(40):1073–1080.

[84] Seither R, Loretan C, Driver K, et al. Vaccination Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten — United States, 2018–19 School Year. MMWR Oct. 18, 2019;68:905–912.

[85] Pingali C, Yankey D, Elam-Evans LD, et al. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13–17 Years — United States, 2020. MMWR Sept. 3, 2021;70:1183–1190.

[86] U.S. Food and Drug Administration. June 3, 2022 Approval Letter – PRIORIX. June 3, 2022.

[87] Krow-Lucal E. Priorix for Prevention of Measles, Mumps, and Rubella – EtR and proposed recommendations. Measles, Mumps, Rubella Vaccines Work Group, Advisory Committee on Immunization Practices (ACIP) June 23, 2022.

[88] Krow-Lucal E, Marin M, Shepersky L, et al. Measles, Mumps, Rubella Vaccine (PRIORIX): Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR Nov. 18, 2022;71:1465–1470.

 

Source: History of Measles Vaccine – National Vaccine Information Center (NVIC)


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