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 [191–193]. Suboptimal seroconversion after vaccination is likely the result of inadequate coverage; improper administration, transport, or storage of vaccine; or age of the vaccine recipients [194–196].

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.

sadly - another: Aliana has SSPE

While social media are a-buzz with stories of a CDC whistleblower - let's remind ourselves why everyone should vaccinate their children (and themselves).

Max, Micha and Natalie have already died. Angelina, who turned 9 years last week, is still fighting. We know their names, because the measles vaccine has significantly reduced the incidence of SSPE, the fatal complication, that shrinks a child's brain, many years after infection.
Now, another girl has been diagnosed - learn her name - celebrate her life - vaccinate your kids, so not one more child has to join the exclusive club:

Aliana was born in early 2010 - a "good measles year" in Germany, with "only" 780 cases. Aliana was one of them - she fell ill as a 6 months old infant, it is not clear who infected her. Then she recovered, at least so it appeared. Aliana grew, she was an open, friendly girl. She quickly found friends, because everyone liked to play with her. In retrospect, she maybe fell more than her peers, but then again, she was still little. But suddenly, Aliana started to forget everything, she couldn't speak as well as she used to. Then, motor problems started, she stumbled, and fell. Unfortunately, the original diagnosis of epilepsy was wrong and 4 weeks ago, Aliana was diagnosed with SSPE. Her grandmother describes the indescribable [my translation from the German]:

I am the granny of a girl who loved life, played games, was friendly to all, and so kind. When I sang songs with her, she immediately knew the lyrics by heart. I could tell you so much more about this little girl, but it breaks my heart how slowly, everything gets lost.

This has to stop! Every case of SSPE, a fate like Aliana's and her family's heartache can be avoided. Check your and your children's vaccination records. Everyone should get/have gotten 2x MMR to protect themselves and babies like Aliana from measles.

A year's worth of measles cases in a week - calling it!

The CDC has just reported the measles cases for 2014 to date: 402 (that is four hundred and two) and 65 cases more than last week. The entire year 2010 only saw 63 cases and in fact, the median number between 2000 and 2010 was 60 per year. How can that be?! Very simple: Every year, measles are imported into the US from abroad. If they are imported into communities with low vaccination coverage, they will spread - usually not very far. Just that this time, measles got imported into a much larger pocket of low vaccination coverage - the Ohio population of Amish. And although these are now vaccinating, there are enough non-immune people around to sustain the outbreak, sustain it big time (I am sure we'll hear a luke warm "that's not an outbreak" from Bob Sears at some point though).

image credit nbcnews

In any case - with 402 cases, the time has come to call it - the last really big outbreak of measles in the US was in 1989 to 1991. Around 55000 people got sick, at least 123 died acutely for a mortality rate of 1 reported death in 451 reported cases. We know that there have been at least 11 SSPE cases due to that outbreak, so the death rate is more like 1 reported death in 414 reported cases. We will reach at least one of these numbers next week. That doesn't mean that someone is going to die next week, statistics don't quite work that way. However, it is, at this point, more likely than not that we'll see a death before the end this year.

I am going to call something else: one someone dies, the anti-vax are going to find something "defective" about the victim, and if it isn't something obvious (like the measles victim in Wales, who reportedly was an underweight adult with a past alcohol problem, so "clearly" not like the vaccine refusers' little snowflakes), they are going to make something up (wrong diet, blabla). No number of deaths will be "enough" for them - sad!

Now is as good a time as ever to check your children's and your own immunization records - 2xMMR is extremely effective in preventing measles and saving lives! Just do it.

Measles Vaccine = Cancer Cure?

Several news outlets reported today that a woman with multiple myeloma has been the first to go into full remission after receiving a "high dose" measles vaccine.  The Star Tribune and Washington Post also report that Stacy Erholtz who had been battling multiple myeloma, a blood cancer, for ten years went into full remission after receiving a single intravenous infusion of an engineered measles virus (MV-NIS).  The measles virus concentration was enough to inoculate ten million people.

Ms. Erholtz reported that it was the easiest treatment by far she had received and experienced a "bad headache" and fever which quickly resolved.  The treatment was performed last year on Ms. Erholtz and another multiple myeloma patient, both selected because they were immune-compromised.  Unfortunately, the other patient's cancer returned after nine months.

Two multiple myeloma patients were chosen because they are immune-compromised, and can't fight off the measles before it has time to attack cancer. Both had limited previous exposure to measles, and therefore fewer antibodies to the virus, and essentially had no remaining treatment options. Of the two subjects in the study, Stacy was the only to reach full remission. The other patient's cancer returned after nine months.

I am reminded of a statement that Dr. Paul Offit made regarding the theoretical antigen capacity that could be handled by a child's immune system and that was described as:

"...babies could theoretically respond to about one hundred thousand vaccines at one time."

Of course that was used by anti-vaxxers as proof that Dr. Offit was evil if he wanted to jab babies with 100,000 vaccines at one time.  But reading comprehension and honesty aren't exactly strong suits of the anti-vaxx disinformation groups.  And now, here we have an immune-compromised woman with multiple myeloma who was given enough measles vaccine that equalled ten million doses intravenously (that's "directly into the bloodstream")...

And it cured her cancer.

In all honesty, it's too soon to predict the success of this new treatment which is entering clinical trials with multiple viruses and types of cancers but for now, one woman is celebrating life cancer-free and there may be new hope for cancer treatments in the near future.