Two new studies add support to measles vaccination

November 30, 2019

Jacob Schor, ND, FABNO

I left naturopathic school in 1991 believing that vaccinations had a negative impact on the function of the immune system and that being immunized came at a cost paid back by with increased risk of autoimmune disease.  Autoimmune disease being a first world problem and infectious disease a third world problem, we rationalized that the risk benefit of vaccination varied with geography.  

In recent years these beliefs have been challenged. The theory that exposure to childhood illnesses was necessary to ‘train’ the immune system to increase its resilience has not held up well over time.  There certainly have been distinct examples of specific vaccines leading to catastrophic autoimmune problems; the 1976 swine flu vaccine led to Guillain-Barre syndrome, the 2009 H1N1 vaccine Pandemrix was associated with narcolepsy [1],   the MMR vaccine causing thrombocytopenic purpura, and smallpox myopericarditis. Yet these reactions have been limited to very specific products and we have not seen general reactions linked to vaccines in general. 

 Instead, examples of vaccination reducing risk of autoimmune disease are showing up in the literature.  Rogers reported in June 2019 that rotavirus vaccination was associated with a lower risk of children developing type 1 diabetes. [2] I am particularly drawn to the publications on measles vaccine because they stand in such stark contrast to where I started decades ago and because watching my mind adjust to this new reality is rather like playing with a mental kaleidoscope where one’s vision of the world is fragmented and tumbled over on itself.

Two studies published in November 2019 have caught my attention.  Both studies examined what is being called immune amnesia that follows measles infection.  The first by Mina et al was published in Science.  [3]  The second by Petrova et al was published in Science Immunology.  [4]  Both studies looked at a cohort of children whose families are members of an Orthodox Protestant community in the Netherlands.  The Netherlands have offered free vaccinations to children since 1957.  As a result, immunization compliance in the country is quite high; about 97% of the population are fully vaccinated.   However, an Orthodox Protestant minority, which has religious objections to vaccination, remains an exception to this norm.  About one quarter of a million people affiliate with these religious groups, about 1.5% of the Dutch population; their members clustergeographically in what we might call a Dutch Bible Belt; a rural area stretching from the south-west to the north-east part of the country. Many of these individuals object to vaccination because of their belief in the doctrine of Divine Providence, that is, the belief that God controls health and disease.  Studies suggest that vaccination rates among this religious sub-population is only about 60%. [5]

In the Mina et al study, 77 unvaccinated children were evaluated both prior to and then 2 months after they had been infected by a measles virus during a measles outbreak that occurred in the Netherlands in 2013.  The children and their families are all members of this Orthodox Protestant community whose parents had opted not to vaccinate them.  Five unimmunized children who had never contracted measles over the course of the study, along with more than 100 other children and adults served as controls. The study authors analyzed the antibody repertoire in these children using a technology called VirScan, which tested the antibodies in the infected children’s blood against antibody targets representing most known human pathogenic viruses.  After measles infection, the children lost on average about 20% of their antibody repertoire. Antibody level drops ranged from 11% to 73% after infection; the biggest drops tended to occur in children with the severest cases of measles.  This effect was not found in the controls.  No loss of antibodies was seen in children after they received a vaccination against measles.[6]

The study by Velislava Petrova should be considered in tandem with Mina’s study.  Blood from 26 of these same children who were part of the Mina cohort was analyzed by a Petrova’s research group.  Their team used genetic sequencing to study the B-cells isolated from the children post infection.  The measles virus is known to infect the B cells that are involved in making antibodies. The measles infection reduced the diversity of memory B cells that recall past infection, and which would normally be quick to fight disease recurrence. The diversity of a second type of B cell, the nonspecific naïve B cells in bone marrow, which normally fight infections unfamiliar to the immune system, also declined. It was as if after a measles infection, the immune system was left in an immature state with a kind of amnesia regarding infections that it had already learned to fight and slow to respond to new infections.[7]

The data from these two studies goes a long way to help us understand multiple observations that have been published over the last decade about the non-specific effects of measles vaccination.

A 2012 Africa study reported that measles vaccine cut deaths from all other infections combined by a third, mainly by protecting against pneumonia, sepsis and diarrhea. In developing countries, measles-vaccinated children have lower mortality rates from all infectious diseases. [8][9]In 2005, Veirum reported that measles vaccinated children had a 49% decreased risk of fatality from infectious disease.  In pneumonia cases there was a 72% decrease risk of dying in the vaccinated children. [10]

One explanation for this protective effect, which was suggested by the Mina and Petrova, is that the vaccine, by lowering measles incidence, prevents damage to immune function. At this point we should not doubt that measles injures the immune system leaving the patient more vulnerable to infection long afterwards.  Mina wrote in 2017 that the “… invisible hallmarks of measles infections [are] increased vulnerability to non-measles infections in nearly all children for weeks, months, or years following acute infections. By depleting measles incidence, vaccination has had important indirect benefits to reduce non-measles mortality.”    [11]

Some research suggests that this immune suppression lasts as long as 30 months and has a profound impact on morbidity.  A June 2019 study used historical medical records to look at three distinct periods of time when past outbreaks of measles and whooping cough overlapped. In a period between 1904 to 1912 risk of whooping cough in those who had measles increased 85-fold. Between 1922 and 1932 whooping cough risk increased 10-fold after a measles infection.  And then between 1946 and 1956, whooping cough risk increased 36-fold post measles infection. [12]

A study of children in the United Kingdom, published in November 2018 compared risk of infectious disease in 2,228 children who had measles against nearly 20,000 children who had not.  Risk of non-measles infections persisted for the full five-years during which the study collected data. During the first month risk of infection was 43% higher in the measles kids but even at five years it was still 15% higher. [13]

There is another possible explanation that may explain the vaccine’s benefit.  Years before this idea that measles causes immune amnesia, there was evidence that the measles vaccine itself acts as an immune stimulant. A 2016 paper described how the measles vaccine activated the immune system in a way similar to Bacille Calmette-Guérin (BCG).  Both lower all-cause mortality through protection against non-targeted pathogens. [14] A March 2019 clinical trial reported that topical application of MMR vaccine in children being treated for juvenile recurrent respiratory papillomatosis (RRP) significantly lowered HPV viral load.[15]

There is a third possible explanation for the vaccine’s benefit, one that may rile some of my dear colleagues; it may be the presence of adjuvants in the vaccine that do the trick. Adjuvants, particularly aluminum, are added into vaccines to stimulate immune reaction. Perhaps it is the aluminum added to measles vaccine that provides protection.   Aluminum is believed to have this effect because it stimulates Th2-type responses and antibody production through B cell activation and by activating the complement system and also by recruiting immune cells to the site of the vaccine injection.  Aluminum promotes antigen uptake by dendritic cells and promotes maturation of these antigen-presenting cells. [16]  Could injections of vaccine adjuvants without the actual disease derived antigens have benefits?  There are several natural plant derived adjuvants that potentially enhance vaccine effects that we have long used alone or together to enhance immune function. Ginseng and astragalus come to mind.[17]

Parents who are wary of vaccinating their children are well represented in our naturopathic patient populations and we are likely to see their unvaccinated children after they have had measles.  We should be mindful that current research has clearly, “… found that measles infection can greatly diminish previously acquired immune memory, potentially leaving individuals at risk for infection by other pathogens.”  

Is there some way to offset this immune amnesia?  The researchers are pondering the wisdom of starting over and vaccinating children who have had measles against all childhood diseases over again. Of course, even if such a practice was proven useful, our patient compliance will be low.

The World Health Organization tells us that “Before the introduction of measles vaccine in 1963 and widespread vaccination, major epidemics occurred approximately every 2–3 years and measles caused an estimated 2.6 million deaths each year. … Global measles deaths have decreased by 80% from an estimated 545,000 in 2000 to 110,000 in 2017.” Furthermore, “During 2000-2017, measles vaccination prevented an estimated 21.1 million deaths making measles vaccine one of the best buys in public health.”[18]

At this point annual deaths due to measles are down to about 100,000 a year.  This alone is enough to tip the scale in favor of continuing vaccination knowing that if public health officials lose control of this disease, the mortality statistics could become far worse.  While measles specific mortality is reported, we are yet to see estimates of morbidity and mortality from other diseases linked to the immune amnesia caused by measles.  Thus, whatever we have thought is the cost of measles, the actual burden is far worse.

As naturopathic physicians we will likely see children post measles infection and we must recognize that their immune systems have taken a hit.  At this point there is no proven approach to restore immune memory or hasten its recovery.  This entire idea of immune amnesia is new enough that we are yet to see even animal trials published investigating possible interventions.  While we probably should encourage revaccination, I can’t imagine such a plan will take root.

Nevertheless, there is one approach we might consider and that is utilizing those saponin containing herbs, in particular licorice, astragalus and ginseng, that stimulate immune function.  The saponin herbs act as adjuvants enhancing immune reaction to disease antigens.  [19][20][21][22][23]  Admittedly, the evidence is weak; at this point this is a ‘won’t hurt, might help’ category of recommendation without any trial derived evidence in support.  Call it a hunch.  


[1]https://www.cdc.gov/vaccinesafety/concerns/history/narcolepsy-flu.html

[2]Rogers MAM, Basu T, Kim C. Lower Incidence Rate of Type 1 Diabetes after Receipt of the Rotavirus Vaccine in the United States,2001-2017. Sci Rep. 2019 Jun 13;9(1):7727

[3]Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljande H, et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens.  Sciences. Vol 366, Issue 6465 01 Nov 2019.

[4]Petrova VN, Sawatsky B, Han AX, et al. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019 Nov 1;4(41). pii: eaay6125. 

[5]Spaan DH, Ruijs WLM, Hautvast JLA TostmannA. Increase in vaccination coverage between subsequent generations of orthodox Protestants in The Netherlands. Eur J Pub Health. Vol 27, Iss 3, Jun 2017, Pgs. 524–530, https://doi.org/10.1093/eurpub/ckw248

[6]Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljande H, et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens.  Sciences. Vol 366, Issue 6465 01 Nov 2019.

[7]Petrova VN, Sawatsky B, Han AX, et al. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019 Nov 1;4(41). pii: eaay6125. 

[8]Aaby MP, Samb B, Simondon F, Seck AM, Knudsen KM, Whittle H. [A non-specific, beneficial effect of measles vaccination. Analysis of mortality studies from developing countries]. Ugeskr Laeger. 1996 Oct 14;158(42):5944-8.

[9]Aaby P, Bhuiya A, Nahar L, Knudsen K, de Francisco A, Strong M. The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh. Int J Epidemiol. 2003 Feb;32(1):106-16.

Free full text: http://ije.oxfordjournals.org/content/32/1/106.long

[10]Veirum JE, Sodemann M, Biai S, Jakobsen M, Garly ML, Hedegaard K, Jensen H, Aaby P. Routine vaccinations associated with divergent effects on female and male mortality at the paediatric ward in Bissau, Guinea-Bissau. Vaccine. 2005 Jan 19;23(9):1197-204.

[11]Mina MJ. Measles, immune suppression and vaccination: direct and indirect nonspecific vaccine benefits. J Infect. 2017 Jun;74 Suppl 1:S10-S17.

[12]Noori N, Rohani P. Quantifying the consequences of measles-induced immune modulation for whooping cough epidemiology. Philos Trans R Soc Lond B Biol Sci. 2019 Jun 24;374(1775):20180270.

[13]Gadroen K, Dodd CN, Masclee GMC, et al. Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK. BMJ Open. 2018 Nov 8;8(11):e021465.

[14]Goodridge HS, Ahmed SS, Curtis N, et al.  Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016 Jun;16(6):392-400. 

[15]Wang Y, Dai PD, Zhang TY. Experimental research on the therapeutic effect of MMR vaccine to juvenile-onset recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol. 2019 Mar;276(3):801-803. 

[16]Aluminium adjuvants used in vaccines versus placebo or no intervention

Cochrane Systematic Review: 24 Sept 2017 

https://doi.org/10.1002/14651858.CD012805

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012805/full

[17]Rajput ZI, Hu SH, Xiao CW, Arijo AG. Adjuvant effects of saponins on animal immune responses. J Zhejiang Univ Sci B. 2007 Mar;8(3):153-61.

[18]https://www.who.int/news-room/fact-sheets/detail/measles

[19]Maqbool B, Wang Y, Cui X, et al. Ginseng stem-leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine. Microbiol Immunol. 2019 Jul;63(7):269-279. 

[20]Zhai L, Li Y, Wang W, Wang Y, Hu S. Effect of oral administration of ginseng stem-and-leaf saponins (GSLS) on the immune responses to Newcastle disease vaccine in chickens. Vaccine. 2011 Jul 12;29(31):5007-14. 

[21]Alexyuk PG, Bogoyavlenskiy AP, Alexyuk MS, et al. Adjuvant activity of multimolecular complexes based on Glycyrrhiza glabra saponins, lipids, and influenza virus glycoproteins. Arch Virol. 2019 Jul;164(7):1793-1803. doi: 10.1007/s00705-019-04273-2. Epub 2019 May 11.

[22]Pickering RJ, Smith SD, Strugnell RA, Wesselingh SL, Webster DE. Crude saponins improve the immune response to an oral plant-made measles vaccine. Vaccine. 2006 Jan 12;24(2):144-50. 

[23]Koczurkiewicz P, Klaś K, Grabowska K, et al. Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug-Minireview of in vitro studies. Phytother Res. 2019 Sep;33(9):2141-2151.