Right now feels like a great time to have a better understanding of waning immunity to vaccines.  What is our experience with other vaccines and waning immunity?  Are the SARSCoV-2 vaccines any better or worse at protecting us over the long term?  Is the prevalence of break-through COVID-19 infections among the vaccinated really any different from what we’ve seen from other vaccines? I’ve been going down a rabbit hole with the MMR vaccine lately precisely because there is a waning immunity issue there, and I am going to force myself to polish up my thinking in a number of posts.  Part of this is driven by my love for science history – reading old papers is my jam – but also, even though my degree is in Immunology, I hadn’t read the original research on any of this until now.  Some of it fits nicely into the way I know the immune system works, but there is a lot that doesn’t, and that is the sweet spot for me.  Caveat: this is not an attempt to write an authoritative account of any of this, its just me reading studies, thinking about them and writing down my thoughts.

In this post I just want to give a short introduction for each of the three viruses in the MMR vaccine.

First M: Measles Virus.

Measles is in the Paramyxoviridae Family of viruses, which are characterized by a (-) strand of RNA for a genome (so the infecting virus must bring in its own RNA polymerase into the cell to make the complementary (+) strand that ribosomes can translate into protein) and that genome is packaged into an enveloped virion decorated by viral glycoproteins.  Something like one in every thousand measles infections will result in encephalitis and death at about that same rate, although my source for those numbers is old (1) its not all that different from the CDCs (frustratingly unreferenced) numbers(6).  Another historical study puts the case fatality rate at something between 6% and 10%, which is frightening (2).  Focusing on the extremes doesn’t give you a good picture though – measles used to put a lot of sick kids into the hospital, placing quite a burden on health care – for those who had health care (I will find a reference on the morbidity of measles later).  Measles’ super power is its transmisability – it is the most infectious human virus we know of.  At least two separate cases during the 80s documented infections in which the patient entered a room 1 hour after the index case (person from whom an outbreak starts) had left (7,8).  It does not infect other species, making it a great candidate for extermination, and recent studies strongly suggest that it originated in the 6th century from a cow virus – rinderpest virus (3).

It was declared eliminated from the United States in 2000, but since then has had resurgences.  At this point, my one sentence summary would be that outbreaks of measles in countries that eliminated it almost always start with someone who was NOT vaccinated (smh) and can, but rarely spreads to vaccinated people.

Second M: Mumps Virus

Mumps virus is also a Paramyxovirus, but belongs to a different Genus  (Rubulavirus) -so at the level I am dealing with, it is very similar in structure and genetics to the measles virus.  Why do we vaccinate against mumps?  I’ll just list the reasons: ~4% of infections end up in sudden hearing loss (4, 5), 0.3% of infections result in encephalitis and the case fatality ratio is about 1.4% (1).  If those seem like small numbers to you, know that there were hundreds of thousands of infections each year in the United States, and if it were just 100,000 infections that would mean 4,000 kids with hearing loss, 300 with encephalitis and 1,400 who are with us no more.  Oh, and it causes orchitis (inflammation of the testicles) – in one outbreak in 1991 in Tennessee, 19% of the infections resulted in orchitis.

Some people might assume that an outbreak in rural Tenessee is the result of not get vaccinated, but they would be wrong.  One of the fascinating parts of this particular rabbit hole is that many Mumps Virus outbreaks occur in highly vaccinated populations – it looks more like a problem of waning immunity than of failure to vaccinate (although that is a problem too).  All kinds of fascinating details I want to get into here.

The R: Rubella Virus

This one belongs to a different Family than the other two – Metonaviridae (this kind of information on viruses, by the way, is at Viral Zone (link), an excellent source of information run by the Swiss Institute of Bioinformatics).  Unlike the other two, rubella virus has a (+) RNA genome (like coronaviruses do) which is able to be translated by ribosomes into protein immediately upon entering the cell.

Why are we vaccinating against it? Birth defects.  To quote the CDC:

Before the rubella vaccination program started in 1969, rubella was a common and widespread infection in the United States. During the last major rubella epidemic in the United States from 1964 to 1965, an estimated 12.5 million people got rubella, 11,000 pregnant women lost their babies, 2,100 newborns died, and 20,000 babies were born with congenital rubella syndrome (CRS). Once the vaccine became widely used, the number of people infected with rubella in the United States dropped dramatically.

One 1965 study found that 1.4% of all African American births in Philidelphia where “significantly affected” by rubellavirus (9).

The fact that rubella virus kind of dropped off the map in the US is what started me on this rabbit hole… here you have one vaccine against three different viruses and what looks like 3 different outcomes.  Measles virus keeps resurging, primarily because of unvaccinated people.  Mumps virus keeps resurging, but primarily because of waning immunity.  Rubella virus, however, just disappears… well, not literally, there are about 10 reported cases per year in the US, measles is frequently above 100 cases per year while mumps is frequently above 1000 cases per year (all numbers there from cases in the United States).

In all three cases, the MMR vaccine has reduced infections to the point where, should we be able to initiate a global vaccination program, its not crazy to think that we could eradicate these viruses.  Before the pandemic, I thought that the major barrier to this was bureaucratic, now it looks like its a far worse problem: irrational thinking and distrust of expertise.

References

(1) – Charensky. 1979 Canadian Family Physician.  Controversies in Immunization.  This guy gives short summaries for the vaccination situation for Smallpox, Rabies, Influenza, Mumps, Polio & Measles – fascinating read.

(2) – Aaby et al. 2022  J. Infect. Measles in the European Past: outbreak of severe measles in an isolated German village 1861.

(3) Dux et al 2020 Science. Measles virus and rinderpest virus divergence dated to the rise of large cities

(4) CDC Vaccines Pink book

(5) Wilson et al 1983. Otolaryngology – Head and Neck Surgery

(6) https://www.cdc.gov/measles/about/faqs.html

(7) Bloch et al 1985. Measles outbreak in a pediatric practice: airborne transmission in an office setting

(8) Remington et al 1985.  Airborne Transmission of Measles in a Physician’s Office

(9) Lindquist et al 1965 British Medical Journal. Congenital rubella syndrome as a systemic infection. Studies of affected infants born in Philadelphia, U.S.A.