Earlier this week, I wrote a post about measles-induced “immune amnesia” and the growing body of evidence supporting it. Afterwards, I was directed to an anti-vaccine “rebuttal” to this evidence (not to my post specifically) which has been making its rounds in anti-vaccine circles and is being presented as a checkmate against the science. The article is titled “Should you be afraid that measles can give you immune amnesia?” by Tetyana Obukhanych, and it has the trappings of being based on evidence, but if you do even a little fact checking, you will quickly realize that its sources are cherry-picked and its arguments blindly disregard large chunks of immunology. Given how popular this article seems to be, I am going to go through it piece by piece and demonstrate that the evidence was cherry-picked and distorted to fit the authors’ preconceptions.

Note: After writing this, I discovered that Orac beat me to the punch by 5 hours. Our overall assessments of the article are quite similar, but he brings up several good points that I did not, so I suggest reading his rebuttal as well.

Before I begin, I want to give an extremely brief overview of the topic being discussed. Scientists have known for several years that an infection with the measles virus causes immune amnesia, in which patients have increased rates of infections and even death from other diseases for several years following the initial measles infection. Recently, studies have shown that this occurs because measles attacks memory lymphocytes (B and T cells) and depletes your body’s antibody repertoire. These memory cells and antibodies are the things that provide lasting immunity. They are specific for particular diseases and persist after an initial infection, thus protecting you into the future. The measles virus destroys these cells, thus leaving you vulnerable to diseases that you were protected against (more details on the immune system here and immune amnesia here). Tetyana Obukhanych disagrees with all of this, but as you’ll see, her evidence is shoddy to say the least.

Note: I will refer to Tetyana Obukhanych by her first name throughout, rather than her last (as one would typically do in academia) simply to avoid creating the illusion that she is on par with the actual scientists whose work I will cite. She’s not. She abandoned rational thought years ago to pursue a career in pseudoscience, so I will not refer to her as if she is a legitimate scientist (see further note at the end of the article).

Moving on to her actual post, she does at least cite studies to support her argument, but, as I frequently write about on this blog, you can cherry-pick a study to support just about any position. Therefore, you have to read the studies critically and look at the entire body of evidence. She did not do this. She simply grabbed a few studies that she liked and ignored multiple much larger studies that discredited her views. Let’s start with the four epidemiological studies she cited as evidence that immune amnesia is not real.

Her first study is Aaby et al. (2002). There are two important things to note about this study. First, it looked at the effects of mild measles infections on long-term survival, but the studies of immune amnesia found that more severe cases resulted in more severe immune amnesia. So, a negative result from a study on mild measles cases is hardly good evidence that immune amnesia is wrong. Second, this study was small for a mortality study (215 children) and the results were just barely significant. In other words, there is a high probability that this is a false positive, and it is far from a compelling result.

Another of her studies is Aaby et al. (1996a). This study looked at both mortality and T cell counts for patients following measles infections compared to controls. For the mortality aspect, the sample size (140 children) was, once again, far too small to have any confidence whatsoever in the results. It is hardly surprising that such a small study failed to find a difference in mortalities. That sample size is, however, reasonable for a study of cell counts; however, the type of counts that were done where quite crude (total lymphocyte count, CD4 percentage, CD8 percentage, etc.). The studies on immune amnesia that Tetyana is trying to refute where were looking at the diversity of memory lymphocytes, but that wasn’t addressed by Aaby et al. (1996a). In other words, this study does not provide any evidence that the studies on immune amnesia are wrong.

Her other two studies (Aaby et al. 1996b; 2003) had more reasonable sample sizes, but they suffered from an inherent problem that was present in all four of these studies. Namely, they were conducted in impoverished areas with little access to healthcare where mortality rates are very high. This is a problem first because it means there are lots of confounding factors at play from other diseases, and second, because it biases the comparison between measles survivors and uninfected (often vaccinated) children. In an area with access to modern medicine, most children survive measles because of the medicine. Thus, the inherent strength of the child’s immune system is fairly irrelevant (unless they are immunocompromised). In areas without modern medicine, however, we inherently expect that children who naturally have stronger immune systems will be more likely to survive the infection. Thus, our population of survivors is biased towards children who naturally have strong immune systems. An absolutely fundamental component of scientific comparisons is that the groups should be alike in every way except for the variable of interest, but that is inherently untrue in these studies. They weren’t simply comparing uninfected children with children who survived measles, rather they were comparing uninfected children with children who were strong enough to survive measles. See the difference? That inherently makes these studies problematic.

The other problem with her use of these papers is simply that they are cherry-picked. She failed to mention, for example, that Aaby also did a study in 1990 (Aaby et al. 1990) that showed substantially higher mortality in the years following measles infection. To be fair, it wasn’t a large study (276 children) and it also had the rural area issues I mentioned, but she should have mentioned it if she was actually giving a fair representation of the literature.

She also utterly failed to mention the massive 2015 study (Mina et al. 2015) that used decades of data from England, Wales, the United States, and Denmark and clearly showed that measles infections increase mortality rates for 2–3 years following infection! This study did a very good job of clearly laying out falsifiable predictions (as science should do), found consistent patterns (as expected for a real result), avoided the survivorship bias inherent in all the Aaby et al. studies, and had large data sets. It is by far the most compelling of any of the studies discussed so far. This is a huge omission on Tetyana’s part and demonstrates obvious cherry-picking. You can’t just pretend that a study like that doesn’t exist.

Further, she declined to mention a massive cohort study in the UK that compared disease rates for 2,228 children following measles infection with 19,930 children who were not infected with measles (Gadroen et al. 2018). They found significant increases in illnesses at every time point for five years after the measles infection. This is another huge study from a developed country, and this form of cohort analysis is generally more robust than the type of population-based analysis used by Mina et al. (2015), but once again, Tetyana failed to mention it. She mentioned the relatively tiny studies from rural areas, but not the massive, robust studies from countries with good health care. It’s almost like she’s deceptively cherry-picking which evidence to show you…

Beyond this epidemiological evidence, we now have several studies showing that measles can infect and kill memory lymphocytes (i.e., the cells responsible for long-term immunity), thus depriving you of your immunity (de Vries et al. 2012; Petrva et al. 2019). In other words, we now have a clear mechanism for immune amnesia that is consistent with and builds on previous research on the ability of certain viruses to target memory cells (Selin 1996; Kim and Welsh. 2004).

She responds to this extremely clear evidence by saying, “So what?  When was it ever proven that immunologic memory has anything to do with protection from re-infection?” Had I been drinking something when I read that, I would have spit it all over my computer. The notion that immunological memory is a key component of protecting people from infections is extremely well-established. It is a fundamental and extremely basic concept of immunology that is literally in every single immunology text book.

Her “evidence” that immunological memory does not protect people is the work of Rolf Zinkernagel which she claims “proves” that immunological memory does not confer protection from disease (she also commits a minor appeal to authority fallacy by unnecessarily pointing out that he is a Nobel prize winner as if that automatically makes him right about everything), and she cites his 2012 review (Zinkernagel 2012). There are several things to unpack here, the first of which is that Zinkernagel is pretty close to alone in his views. Indeed, in his papers, he readily acknowledges that the vast majority of immunologists disagree with him and his interpretation of the data. Also, he has been arguing for his view for a long time (since at least the late 1990s) and has not been able to convince many immunologists that he is right (because he lacks sufficient data), and that review from 2012 has a grand total of 21 citations (not much for a review that claims to overturn a massive component of immunology), and even the papers citing him argue that immune memory is important for being protected from diseases, they just point out that there are caveats and some special situations for certain pathogens (see Hohman and Peters [2019], for example). So Tetyana essentially wants us to accept that all of immunology is wrong because this one man says so. That’s going to be a hard pass from me. That’s simply not how science works.

To be clear, the fact that Zinkernagel’s views have not been widely adopted does not automatically make him wrong (but it is suggestive). Rather, the issue is simply that the evidence does not appear to be on his side. That 2012 review, for example, was not a systematic review (i.e., one that considers all literature on a topic). Rather, it was a critical review, which means that he gets to pick and choose which papers to include to build the argument that he wants to. In contrast, a systematic review of the literature (specifically looking at memory T cells and their effect on disease) looked at 147 studies covering 25 human disease and found that immunological memory is indeed very important in providing protection from disease (Muruganandah et al. 2018). There’s also lots of other reviews (not all systematic) either on immunological memory or that talk about it and explain that it is real and important (e.g., Macallan et al. 2017; Pennock et al. 2013; Pulendran and Ahmed 2006), and, as I said, this is covered in literally every text book on immunology.

Having said all of that, I actually think that Tetyana is somewhat misinterpreting Zinkernagel. To be fair, I did as well the first time that I read the 2012 review, and Zinkernagel certainly hasn’t done himself any favors in how he has written his arguments. Following my confusion with his 2012 review, I read his 2018 critical review, which is essentially the same paper and still (in my opinion) fails to provide compelling evidence for his position, but it made a bit more sense. Then I started reading his older papers and finally think I figured out what he is actually arguing. Consider this quote from a paper (Ochsenbein et al. 2000) that he was an author on,

“Therefore, for vaccines to induce long-term protective antibody titers, they need to repeatedly provide, or continuously maintain, antigen in minimal quantities over a prolonged time period in secondary lymphoid organs or the bone marrow for sufficient numbers of long-lived memory B cells to mature to short-lived plasma cells.”

His argument, as I understand it, is that memory cells alone are not sufficient for protection. Rather, they need to constantly be replicating and maturing into active cells that produce antibodies, and it is the population of active cells (and their antibodies) that actually provides the protection, but for this population to be maintained, a low level of antigens (the surface recognition molecules that identify a given pathogen) must be present to stimulate the memory cells. I’m still not convinced that he’s right, but this makes a lot more sense than simply saying that immunological memory is unimportant for protection. Indeed, other complex interactions between the innate immune system and the adaptive immune system have certainly been documented (e.g., Castellino et al. 2009). If I am interpreting him correctly, then the argument is not that memory lymphocytes are not important, but rather that they alone are not sufficient, and after the initial infection, there is a perpetual cycle of antigens stimulating the memory cells, resulting in the production of antibodies, effector cells, etc. This means that, contrary to what Tetyana is arguing, those memory lymphocytes are critically important. If they get taken out by a disease like measles, then they cycle will be broken because they will no longer be there to mature into the active cells that Zinkernagel argues are responsible for protection, meaning that you will, once again, be back to being unprotected. Thus, even if Zinkernagel is right, Tetyana’s argument is wrong (she later cites another of his papers [Steinhoff et al. 1995], but just refer back to this section for that; sufficient to say she is extrapolating far beyond what we can actually conclude from the paper).

On a quick side note, I am curious about why Tetyana didn’t cite Zinkernagel’s more up-to-date 2018 review. I have to wonder if it is because he spoke disparagingly of “vaccine deniers” in the abstract. You see, Zinkernagel is no anti-vaccer, and here we can see another example of the inconsistencies of the anti-vaccine mindset. According to Tetyana, we should blindly believe him instead of virtually all other immunologists when it comes to immune memory (after all, he won a Nobel prize), but when it comes to vaccines, we should ignore him and his Nobel prize. This is classic cherry-picking of experts and even the views of an expert.

Next, we get to her response to the Mina et al. (2019) which found that measles infections reduce the diversity of circulating antibodies for diseases that you were previously protected against. As before, she responds to this by denying immunology 101. She asks, “When was it ever proven that antibodies offer protection?” Questions like this are baffling to me. Yes, antibodies can offer protection! This is extremely well established. To give probably the most well-known example, newborns get antibodies from their mother, and those antibodies protect them until their own immune system builds up memory for the common pathogens around it (Niewiesk 2014; van der Lubbe et al. 2017). This is really basic stuff. Sure, there are complexities and interactions among different parts of the immune system, and different diseases require different immune responses, but pretending that antibodies aren’t important for protection is either insane or dishonest. Further, even some of the papers she cites says this. For example, she totally ignores the numerous times that Zinkernagel discusses the importance of antibodies in offering protecting. Let me quote the abstract of his 1995 paper (Steinhoff et al. 1995) that she somehow thinks proves her point (my emphasis)

“Adoptive transfer experiments showed that neutralizing antibodies against the glycoprotein of VSV (VSV-G) protected these mice efficiently against systemic infection and against peripheral subcutaneous infection.”

Similarly, remember that 2012 review that she is so found of? Here is a quote from its abstract (again, my emphasis)

“Protection depends on pre-existing neutralizing antibodies or pre-activated T cells at the time of infection.”

Sure seems like her man Zinkernagel thinks that antibodies provide protection. To be clear here, I’m not saying that antibodies provide protection because Zinkernagel says they do, rather, I am trying to demonstrate the absurd levels of cherry-picking she is going through. Her own sources defeat her arguments.

Further, her “evidence” that all of immunology is wrong about antibodies is simply a report of four healthcare workers who became infected with measles despite having measles antibodies (Ammari et al. 1993). Now it’s my turn to ask, “so what?” No one has ever said that having detectable circulating antibodies is a 100% guarantee that you won’t get the disease, especially for someone like a healthcare worker who will be exposed to it regularly. Further, as eluded to earlier, different diseases are most effectively targeted by different parts of the immune system. So even if antibodies provided 0 protection against measles (which is not the case) that would not change the fact that they are very effective for many other diseases, meaning that it is a big problem when an infection with measles reduces their diversity.

Additionally, with regards to her arguments about both immunological memory and antibodies, keep in mind that we do have large epidemiological studies showing that measles-induced immune amnesia is a real thing that increases infections and death for several years following measles infections. This is a fundamental point that she totally ignores. We aren’t talking about hypothetical mechanisms here. Rather, the recent studies were looking for a mechanism to explain a phenomenon that was already established!

She rambles on for a while about a few other points that are fairly irrelevant, so I’ll just quickly comment on two of them. First, she suggests that the chicken pox virus likely can target memory cells as well and asks why people aren’t freaking out about it, as if that somehow proves her point. First, people aren’t freaking out about it because scientists are a cautious bunch and don’t like jumping to the conclusion that the effects of one virus will be the same as the effects of another. Right now, we only have good data for measles. Second, it is likely that chicken pox can do something similar, but that is simply a good argument for getting the chicken pox vaccine! It doesn’t discredit the science or alleviate the concern.

The other thing I want to comment on is one of her last paragraphs where she seems to suggest that measles infection is good because, if it kills memory cells, it should alleviate allergies and asthma. I’m not convinced that infection would alleviate allergies, but let’s assume for a minute that it does. We have epidemiological data clearly showing that mortalities increase for 2–3 years following measles infections, and she thinks this is overridden by a possible reduction in allergies? Further, let’s not forget that measles is itself deadly. Those Aaby et al. studies she cited showed that. Are we just supposed to pretend that it isn’t deadly? As an adult with allergies, I prefer a life of daily antihistamines (allergy meds) to a childhood death from a disease, thank you very much.

Conclusion

In short, Tetyana’s post is a whole lot of nonsense. It cherry-picked its evidence, relied on a fundamental lack of understanding of basic immunology, and ignored clear epidemiological evidence that measles-induced immune amnesia is a real thing with deadly consequences. The actual evidence overwhelmingly supports immune amnesia and shows that the beneficial effects of the measles vaccine go far beyond simply preventing measles.

A note about Tetyana Obukhanych and appeals to authority

 I put this after the main article, because it is tangential, but I do want to make a quick comment about the way anti-vaccers respond to Tetyana. Much to my surprise, she actually does have a PhD in immunology. This does not, however, automatically mean that she knows what she is talking about. Having a PhD (or any advanced degree) does not guarantee that someone is smart or even particularly knowledgeable. Further, as far as I can tell, she only ever published 8 papers, and hasn’t published any research since 2012, when she left academia to pursue a career writing anti-vaccine books and posts, giving talks, and offering online pseudoscience courses. None of this automatically makes her wrong, of course. My point is simply that you shouldn’t be lulled into a false confidence in her views just because her name has the letters “PhD” after it. Indeed, after leaving academia, she has gained a reputation for writing highly counter-factual posts that are devoid of reasoning (here are examples of other skeptics debunking some of her previous writing: Skeptical Raptor, Science-Based Medicine, and Snopes). Again, this doesn’t automatically make her wrong about immune amnesia. Rather, I am simply pointing out that she is not particularly reputable, and she certainly isn’t the world-renowned immunologists that many anti-vaccers seem to think she is (also, see this post by Vaxopedia).

Related posts

• Research, you’re doing it wrong: A look at Tenpenny’s “Vaccine Research Library”
• Vaccines and autism: A thorough review of the evidence (2019 update)
• Vaccines don’t “bypass the immune system”
• Vaccines don’t give lifelong immunity, but they are still better than natural immunity
• Vaccine injuries and confirmation biases

Literature cited

(some of these are behind paywalls, see this post for suggestions on how to access them)

• Aaby et al. 1990. Delayed excess mortality after exposure to measles during the first six months of life. AM j Epidemiol 132:211.
• Aaby et al. 1996 No persistent T lymphocyte immunosuppression or increased mortality after measles infection: a community study from Guinea-Bissau. Pediatr Infect Dis J 12:39–44.
• Aaby et al. 1996b. No long-term excess mortality after measles infection: a community study from Senegal. Am J Epidemiol 143:1035–1041.
• Aaby et al. 2003. 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 32:106–116
• Aaby et al. 2002. Low mortality after mild measles infection compared to uninfected children in rural West Africa. Vaccine 22:120–126.
• Castellino et al. 2009. Generating memory with vaccination. European Journal of Immunology 39: 2100–2105
• Gadroen et al. 2018. Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK. BMJ 8
• Hohman and Peters. 2019. CD4+TCell-Mediated immunity against the phagosomal pathogen Leishmania: Implications for vaccination. Trends Parasitology
• Kim and Welsh. 2004. Comprehensive early and lasting loss of memory CD8 T cells and functional memory during acute and persistent viral infections. J. Immunol. 172: 3139–3150
• van der Lubbe et al. 2017. Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization. Virology Journal 12:1695
• Macallan et al. 2017. Human T cell memory: A dynamic view. Vaccines 2017: 5.
• Mina et al. 2015. Long-lasting measles-induced immunomodulation increases overall childhood infectious disease mortality. Science 348: 694–699.
• Mina et al. 2019. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science 366:599–606
• Muruganandah et al. 2018. A systematic review: The role of resident memory T cells in infectious diseases and their relevance for vaccine development. Frontiers in Immunology 9:1574
• Niewiesk 2014. Maternal antibodies: Clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Frontiers in Immunology 5:446.
• Ochsenbein et al. 2000. Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs. PNAS 97: 13263-13268.
• Pennock et al. 2013. T cell responses: naïve to memory and everything in between. Adv Physiol Educ 37: 273­–283.
• Petrva et al. 2019. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Science Immunology 4: eaay6125
• Pulendran and Ahmed 2006. Translating innate immunity into immunological memory: Implications for vaccine development. Cell 124: 849–863
• Selin 1996. Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections. J. Exp. Med. 183: 2489–2499
• Steinhoff et al. 1995. Antiviral protection by vesicular stomatitis virus-specific antibodies in alpha/beta interferon receptor-deficient mice. J Virol 69:2153–2158.
• de Vries et al. 2012. Measles immune suppression: Lessons from the macaque model. PLOS Pathog. 8: e1002885
• Zinkernagel 2012. Immunological memory ≠ protective immunity. Cellular and Molecular Life Sciences 69:1635–1640
• Zinkernagel 2018. What if protective immunity is antigen—driven and not due to so-called memory” B and T cells? Immunological Reviews 2018: 283–246.