Immune Response To Vaccination

How does the human immune system react to vaccination to confer immunity?  Using Yellow Fever vaccine, it has been shown that certain T cells divide within the first two weeks after exposure to the antigen and thereafter slowly divide, with an epigenetic profile allowing for rapid response upon re-exposure to the antigen.  Abstract:

The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen.

Ovarian Cancer Vaccine

Personalized cancer vaccine for ovarian cancer; abstract:

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.

A Bizarre Story For Friday The Thirteenth

Unauthorized vaccine for herpes:

A Southern Illinois University professor is being investigating for allegedly injecting people with an unauthorized vaccine for herpes.

The FDA is investigating William Halford for administering his experimental vaccine to patients without safety oversight from the organization or an institutional review board. Halford, who died in June, gave participants the vaccine in St. Kitts and Nevis, islands in the southern Caribbean, in 2016, and in Illinois hotel rooms in 2013, Kaiser Health News reported.

The professor, 48, gave the vaccine to at least 20 herpes patients in St. Kitts and Nevis and to at least eight herpes patients at a Holiday Inn Express and a Crown Plaza Hotel near his research lab at the university in Carbondale, Illinois.

Authorities are uncertain where Halford manufactured the vaccine.

Now, the FDA's Office of Criminal Investigations is looking into whether people at Halford's former company, Rational Vaccines, or Southern Illinois University had knowledge of his actions and violated FDA regulations by assisting him in unauthorized research, four people familiar with the situation told Kaiser Health News.

Although the FDA rarely prosecutes research violations, the agency may move forward with this case and pursue the unauthorized development of the vaccine as a crime. These violations are severe because Halford is not a medical doctor and provided an experimental vaccine without supervision, which is a possible violation of human-subject guidelines.

The university told Kaiser Health News it's cooperating with the FDA's investigation and admitted Halford violated university rules and the law. However, university officials deny any knowledge of his actions and say they are not responsible, the sources said.

Rational Vaccines did not comment. The company assisted in the Caribbean trial but was not founded at the time the hotel-room injections occurred.

Microbiotic Importance

By Darryl Leja, NHGRI - http://www.genome.gov/dmd/img.cfm?node=Photos/Graphics&id=85320, Public Domain, https://commons.wikimedia.org/w/index.php?curid=29534265

Here is a review once again stressing the importance of the microbiota for human health, concentrating on immune system effects that influence “host response to infection, vaccination and cancer, as well as susceptibility to autoimmune and neurodegenerative disorders."  Abstract:

The study of the intestinal microbiota has begun to shift from cataloging individual members of the commensal community to understanding their contributions to the physiology of the host organism in health and disease. Here, we review the effects of the microbiome on innate and adaptive immunological players from epithelial cells and antigen-presenting cells to innate lymphoid cells and regulatory T cells. We discuss recent studies that have identified diverse microbiota-derived bioactive molecules and their effects on inflammation within the intestine and distally at sites as anatomically remote as the brain. Finally, we highlight new insights into how the microbiome influences the host response to infection, vaccination and cancer, as well as susceptibility to autoimmune and neurodegenerative disorders.

My Measles Experience

Left, child with measles (not me).

https://commons.wikimedia.org/wiki/File:RougeoleDP.jpg

This is going to be a controversial post, since I know there are folks with strong opinions on this topic, and I also know there are other blogs similar to this one that take a different view than mine.

In general, I support vaccination.

In particular, I had no hesitation in having my daughter get her MMR vaccinations, which are looked upon with suspicion by some.

I had the measles myself.  My parents did their due diligence and had me vaccinated, but that was in the old days when two fundamental errors were made.  First, the vaccine (to measles alone at that time) was an inactivated vaccine (unlike the live MMR) and was weakly immunogenic. Second, at that time, this inferior vaccine was given to children under the age of one, when there could still be maternal antibodies in the child that would suppress the child’s own immune response to the vaccine. Essentially, it was the equivalent of vaccinating me with saline - no immune response.  

At the age of 12, I was exposed to a group of younger children some of whom I suspect were not vaccinated (another story). I note that the MMR was available at that time, but my family doctor didn't think older children like me needed it, since I was "already vaccinated".

So I got the measles.  That was not fun - that was by far the most sick I have been, including several days with a fever reaching 105 degrees F.  I missed several weeks of school, much of that time spent in bed, took a long time to recover, and remember having some faded marks on my arms from the rash for long time afterward.  At one point, my parents were worried whether I would recover at all.  

Sparing children that ordeal is a good thing.  I also had the mumps as a child, not as bad as the measles, I was moderately sick, and I remember that at least one of my neck glands was swollen so I looked like a hamster with a stuffed cheek pouch.  For adult men however, mumps can be more of a problem.  I also had the chicken pox, annoying and no fun, but less intense than the measles (and mumps).  

I've had a more recent MMR vaccination myself - college admission required it, and they didn't care that I had doctor's records of the disease. Recently I decided, for fun, to have my MMR antibody titer checked. Considering that I had the measles and the mumps, and was subsequently vaccinated as well, it was no surprise that my antibody levels for these diseases were sky-high.

In any case, we seem to forget about these illnesses because of the effectiveness of current vaccines, but at one time they were a scourge.  To me, the vaccination is better than the disease.   That's my "two cents."