Tuesday, February 17, 2015

The Measles Vaccines (MMR and MMRV) Protect Against Measles


Photo: http://imgbuddy.com/measles-virus-picture.asp


A new anti-vaxx myth has surfaced which seems to have been developed as a result of my recent blogpost Disneyland Measles Outbreak is Due to Measles which discussed the measles genotype responsible (hint: it wasn't the vaccine strain).  Some, with no knowledge of virology nor immunology are spreading the myth that since the measles strain in the MMR vaccine is genotype A that it couldn't possibly protect against measles genotype B3 which is the genotype responsible for the latest U.S. outbreak and has spread to Mexico and Canada.  I will discuss how and why MMR vaccines are cross-protective for wild-type measles strains.

First there is some terminology which must be understood to follow along:
Serotype: Microorganisms of the same species can be further divided into serotypes, serovars or sub-groups based upon their surface antigens.

Antigen: A structural protein on the surface of a pathogen that is able to recognise cell receptors on the surface of a host cell.  The antigen is also the part of the pathogen which provokes the host adaptive immune response that generates antibodies.

Epitope: The very specific part of the antigen which antibodies attach to.

Genotype: The nucleotide sequence of certain regions of a viral genome which classifies differences.

The measles virus has only one serotype and causes measles unlike Human Papillomavirus which has dozens of serotypes and can cause different diseases.  This is why we see multiple serotypes included in the HPV vaccine and only one strain in each of the available measles vaccines which are all genotype A.
Many of the attenuated strains in use are derived from the Edmonston strain isolated in 1954, including the Schwartz, the Edmonston-Zagreb, and the Moraten strains. Other strains which are not derived from Edmonston strain include the CAM-70, TD 97, Leningrad-16, and Shanghai 191 (Ji-191) strains.
Measles virus genotypes are based upon their nucleotide sequences at the least conserved regions of the viral genome:
Wild-type measles viruses have been divided into distinct genetic groups, referred to as genotypes, based on the nucleotide sequences of their hemagglutinin (H) and nucleoprotein (N) genes, which are the most variable genes on the viral genome.
The 450 nucleotides encoding the carboxy-terminal 150 amino acids of the nucleoprotein has up to 12% nucleotide variation between genotypes. The 450 nucleotides that encode the carboxy-terminal region of the nucleoprotein (N–450) are required for determination of the genotype. The measles genotyping protocol is available from CDC.

Photo: http://download.thelancet.com/images/journalimages/0140-6736/PIIS0140673610623525.gr3.lrg.jpg

What this means is that whenever a measles case occurs, a sample (throat or nasal swab) is taken from the patient, submitted to RT-PCR (reverse transcription-polymerase chain reaction) and PCR (polymerase chain reaction) which are molecular techniques to essentially isolate amplify the number of DNA copies so that they can be sequenced.  DNA sequencing determines the nucleotide sequences of specific genome regions and then compared to other isolates to see where the measles virus came from and also mutations that may have accumulated.

Recovered measles viruses are constantly monitored, tested and characterised to identify areas of the genome which may antigenically-drift.  Circulating measles viruses have also been tested against vaccine-derived antibodies to ensure vaccines will cross-protect against the numerous genotypes that are imported.  This is achieved through virus neutralisation assays for example.  This is a test that combines measles genotypes with serum samples of people either vaccinated or previously infected with wild-type measles to determine if antibody binding occurs.  A fluorescent tag is added and then the antibody-antigen complex is measured. Results of various assays demonstrate that vaccine-derived antibodies protect against many different measles genotypes:
The serum samples from recently vaccinated persons neutralized both the Moraten and Chicago-I viruses equally well (table 1): There was a less than 2-fold difference in neutralization titers. In contrast, serum samples from persons with a recent wild type infection were able to detect antigenic differences between the viruses. Sera in this set had neutralization titers against Chicago-l that were 4-8 times higher (average, 5.1) than the titers against the vaccine strain.
Very specific antibodies called monoclonal antibodies (MAbs) are also developed and tested against measles viruses including the vaccine strains to monitor vaccine efficacy and antigenic drift of measles genotypes:
Overall, the antigenic data indicated that some epitopes have been conserved between the vaccine strain and the recent wild type viruses, while others are unique to the recent wild type virus. The H and F proteins are responsible for the induction of a neutralizing antibody response to measles virus. Therefore, the antigenic differences were most likely due to variation in these surface glycoproteins. 

Protection against the current circulation measles genotype, B3 has been elucidated.  In other words, studies have been and are conducted to test antibodies derived from vaccination against numerous wild-type measles viruses.  Measles genotype B3 which is the currently circulating strain in the U.S., is neutralised by vaccine-derived antibodies.  That, in turn, means that the virus can't bind to host (human) cell receptors and cause disease.
On the basis of the sequences of their N and H genes, MeVs can be assigned to 1 of 23 genotypes and 1 provisional genotype [11, 12]. All vaccine strains and their wild-type progenitors are assigned to genotype A. Experiments with monoclonal antibodies have defined antigenic differences between the H proteins of genotype A vaccines and the H proteins of wild-type viruses grouped in other genotypes [62, 188, 189]. However, there is only 1 serotype for measles, and serum samples from vaccinees neutralize viruses from a wide range of genotypes, albeit with different neutralization titers [188, 190] More importantly, despite the presence of different endemic genotypes, vaccination programs with standard measles vaccines have been successful in every country where they were performed adequately [191193]. Suboptimal seroconversion after vaccination is likely the result of inadequate coverage; improper administration, transport, or storage of vaccine; or age of the vaccine recipients [194196].
It's a bit of a complex issue to digest but some key points are that measles vaccines induce many different antibodies against measles antigens.  There is some antigenic drift that renders a single antibody insufficient binding to a single antigen from some wild-type measles viruses but over all, vaccines protect us from many different genotypes including the currently circulating B3 genotype. The epidemiology of the measles outbreak also demonstrates the effectiveness of the MMR vaccine.  To date there have been 141 cases confirmed (dozens more reported) by the CDC. Measles is one of the most infectious diseases known and this interactive graphic demonstrates how measles can spread in variable susceptible populations.  If the vaccine did not proffer cross-protection, there would be tens of thousands of cases to date.  Obviously this is not the case as the majority of cases are unvaccinated.

A more easily-digestible version of this has been posted at The Scientific Parent.

17 comments:

  1. 141 now http://www.cdc.gov/measles/cases-outbreaks.html

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  2. Sir, Im a student of Community Medicine from India. My doubt is whether the components in the MMR vaccine, i.e. the measles, mumps and rubella are cross-protective, all the three being members of the Myxoviridae group.

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    1. If I understand correctly you are questioning whether measles, mumps and rubella vaccines are cross-protective for one another. The answer is no, not only are they of different families (measles and mumps belong to Myxoviridae while rubella is in the Togaviridae family) but are different genus and species.

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  3. I believe the answer to your question is no - the three vaccines protect separately for each illness.

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  4. Finally one death from measles in the "Western world" Don't quote third world figures. You don't ever mention the downside of measles vaccine. There are over 20 infant deaths every year from the mmr vaccine every year in just the U.S. and thousands of neurological problems and much more. And U.S. gov pays compensation.
    http://www.cbsnews.com/news/vaccines-autism-and-brain-damage-whats-in-a-name/
    For all the real science against vaccines see.
    www.vaccinesaftey.blogspot.com

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    1. You should stop parroting the nonsense you read on anti-vaccine websites. Those "deaths" were not verified.

      Again, the reason there is very low measles mortality in the USA is because of very low measles morbidity... you can't die of a disease you don't get because the MMR vaccine works for you!

      If you have real evidence the MMR vaccine, which was introduced in the USA in 1971, causes more harm than measles, mumps and rubella, then provide the PubMed indexed studies by reputable qualified researchers. Not some random website from someone who does not know the difference between mortality and morbidity. It just makes you look foolish, especially after it has been explained to you.

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    2. Typical Pharmaceutical pusher response. My Data is from the CDC's own VAERS site. Yes I know it is not cause and effect, But doctors who put ( 86%of entrys are by doctors)in the data would not put in a adverse event unless he believed event was caused by a vaccine. So you can't just ignore the data, though that is what you people do.
      http://www.medalerts.org/analysis/archives/561
      http://www.medalerts.org/analysis/archives/628
      I can tell by your response you are a Big Pharma paid troll, you did not look at the links I supplied. You just knock everything, don't care about the kids, just money. For others out there this site explains everything. When vaccines supposedly saved millions we had 4 vaccines to take. In 1995 we had 5 in in kids schedule. in 2005 we had 8, now we have 14!! Do we nee the last 9?? See
      http://www.vaccinesaftey.blogspot.ca

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    3. You don't even know the difference between morbidity and mortality, and why it is important. You are both close minded and clueless.

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    4. "I can tell by your response you are a Big Pharma paid troll"

      How so? By telling you that your website has several problems? By the way the MMR vaccine has been on the American pediatric schedule since 1971, so it is not a new vaccine.

      Instead of learning and correcting your errors you pulled out the old and boring Pharma Shill Gambit.

      Now just go away until you learn what are and are not valid science sources (not most of your links, especially "childhealthsafety), and why it is important to learn the difference between mortality and morbidity. Hint: the paper titled "Trends in Infectious Disease Mortality in the United States During the 20th Century" does not show the decline of disease incidence.

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    5. My Data is from the CDC's own VAERS site. Yes I know it is not cause and effect, But doctors who put ( 86%of entrys are by doctors)in the data would not put in a adverse event unless he believed event was caused by a vaccine. So you can't just ignore the data, though that is what you people do.
      No Ms. Toff, Anyone can make a VAERS entry and they aren't believed to be vaccine-derived by the majority of physicians. Add to that duplicate and triplicate entries along with second and third hand reports and VAERS is useless to use to claim deaths from a vaccine.

      By the way, who pays you? Big Stupid Vaccine Conspiracy Nutters?

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    6. Ah I thought so. Thanks Science Mom. Obviously this whole site is a Big Pharma sponsored site pushing there agenda.
      Also by the above responses I can tell no one read all the links I presented. Good by, I am sure you will be happy to know you won't here from me again.

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    7. "Also by the above responses I can tell no one read all the links I presented"

      Actually I am familiar with many of them. It was quite clear you had not read the JAMA article you claimed showed the diseases went down, it it was only about mortality. Even though I explained to you on the other thread, and mentioned it a couple times over... you still don't understand why mortality and morbidity are two completely different things.

      Seriously, why do you think an article discussing the reduction of disease mortality due to improved medical care is about the reduction of the number of disease cases?

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    8. Very good that we won't "hear" back from you again....since you are definitely incapable of recognizing the difference between incidence rates and mortality rates.

      Moreover, the "shill gambit" is old and tired. I am always amazed that Anti-Vaxers are incapable of understanding that people can look at all of the available evidence and come to a conclusion that is different for their own - so instead, they claim that those people are somehow "paid" to hold those opinions.

      Because it makes just as much sense to claim that anti-vaxers are paid minions of the Health Industry - since it is abundantly clear that it is much more profitable to treat diseases than it is to prevent them via vaccines.

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    9. "So you can't just ignore the data, though that is what you people do."


      of course VAERS reported death are NOT ignored!!!
      VAERS reports, especially those of death, are thorougly investigated by the CDC. They will contact the attending doctors, and the family, make a case study, look for common patterns and statistically significant occurences of common reactions. Thats the whole point.

      This is not, of course, something that you or I or even a doctor can do on his own. But thats OK, its only done once, and the conclusion of the investigation are made public.

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    10. "In 1995 we had 5 in in kids schedule. in 2005 we had 8, now we have 14!! Do we nee the last 9??"

      That's a triumph! Each vaccine is a another desease we don't get. We have a ton of things now we didn't have 50 years ago that make our lifes better. But none as much as vaccines.

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    11. Nobody develops a vaccine "just because."

      These diseases afflicted hundreds of thousands, if not millions of people...

      And yes, there are a lot of vaccines in the pipeline, but given the rigorous FDA clinical trial and approval process, maybe 1 out of 50 or even 1 out of 100 will actually make it to market.

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