From: The Chief Scientist of New York University’s
Experimental Pathology, Immunology and Pathogenesis
of Autoimmune and Allergic Disease Research Team: November 06, 2013

“Dear Dr. Hines,

I am traveling now and under time constraints to be able to reply carefully to your mail. In principle, I agree that body weight should be a consideration when deciding the amount of antigen or vaccine to be administered, and I am surprised that it wasn't a factor in the Leptospira vaccine tests. Once animals have been sensitized and produced IgE, most certainly, upon re-exposure, the dose of antigen becomes crucial to diminish the impact of an anaphylactic reaction, certainly a high dose per body weight would lead to death much more than a low dose of the same antigen and this would be proportional to the weight of the animal.
I will reply more carefully to your email once I get back to New York in two weeks.”

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From: The Director,
Center for Immunology
Department of Microbiology
University of Minnesota: November 04, 2013

“Dear Dr. Hines,

High antigen doses cause naive CD4+ T cells to differentiate most efficiently into Tfh, thereby helping B cells secrete large amounts of isotype switched antibodies, perhaps including IgE. Such a scenario could lead to anaphylaxis. “

[The plausibility of that explaination was confirmed to me as well by a vaccine scientist at the NIAID/LID ]

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From: The Chief Scientist
Center For Disease Control
Anthrax Vaccine Development Unit
CDC Atlanta, GA : October 29, 2013

“Dear Dr Hines,

My apologies for the delay in following up.
When we administer varying dilutions of the anthrax vaccine adsorbed (AVA, BioThrax) or graded antigen loads of recombinant protective antigen (rPA) in animals, we do indeed see a modulation of the magnitude of the anti-PA IgG response, though we do not seem to see a similarly striking modulation of the cellular immune response.
In rhesus macaques administered a 1/5 dilution of AVA (volume adjusted in saline) we see a magnitude of anti-PA IgG response similar to that seen in humans receiving a full dose.”

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From: The Chief Leptospirosis Scientist
Veterinary Laboratories Agency
Surrey, UK: November 04, 2013

“Dear Dr. Hines,

Apologies for not replying earlier, things have been a bit hectic finishing off at Manchester Uni. When assessing vaccines we dilute them 1/40 to account for the differences in size between dogs and hamsters... I was under the impression that the European pharmacopoeia came up with this figure but whether or not they used allometric scaling I couldn't say!  “

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From: The Chairman of The Department of
Epidemiology of Microbial Diseases
Yale School of Public Health: November 04, 2013

“Dear Ron
As you mention, the adverse reactions of bacterin-based vaccines which you describe are well known both in animals and humans, yet the producers (at least the ones that I have met in Cuba for human vaccines, and veterinary companies) formally deny that there are any problems, although informally they say they know this occurs.  At least one company has been focusing on sub unit vaccines because of complaints with the bacterin based vaccines from owners.  Again, nothing published that I know of on this problem (on the contrary what is published usually states the low rate of adverse reactions). 
I am guessing that the main problem in using reduced doses in dogs (to prevent adverse reactions) is the rather costly process of providing evidence of efficacy in the standard animal models for the use of these reduced doses, and then establishing the QC/QA for this target endpoint in their lots.  This may be the reason for their resistance. “
[sugar cane workers in Cuba are vaccinated against leptospirosis]

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From: a Principal Vaccine Scientist
Intervet/Schering-Plough Animal Health: October 31, 2013

Dear Dr. Hines,

The majority of the activation and maturation of B cells into either memory B cells or plasma cells occurs in the draining (most proximal) lymph nodes to the injection site.  That being said there can be systemic activation to a lesser extent in non-draining lymph nodes and spleen.  Excess antigen will either be carried away through afferent channels if not processed in the lymph node or be processed by innate phagocytic cells and possibly not be involved in adaptive immunity (there is always a balance).  Tolerance [anergy] can be achieved if the antigen is in excess enough or if there are multiple injections such to induce tolerance.  Articles from Rolf Zinkernagel's group I think discuss some of these principles in much greater detail.  Marc Jenkin's group also looks at T cell activation but their thoughts are that antigen can be circulating for lifetimes (in models) that continually keep activation of small amounts of memory T cells too.  Adjuvants always alter the fates of the antigen as well so that is another caveat to keep in mind. “

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From: The Director,
Johns Hopkins Center for Autoimmune Disease Research
The Johns Hopkins Medical institutions
Baltimore, MD : October 05, 2013
 
“ Dear Dr. Hines,

I am traveling and do not have any references at hand, but our practice is to scale the antigen dose to the weight of the animal.”

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From: The Director of Clinical Research on Immunology and Inflammatory Disease Harvard Medical School/Massachusetts General Hospital : 12/01/2013

" Dear Dr. Hines

Certainly, vaccines may induce untoward immune responses, and this has generally not been tested nearly as well in animals as in humans. It sounds like you have learned to adjust vaccine dosages for smaller animals, which seems reasonable to me."

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From: The Director of the Australian Research Council's Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Melbourne

"There is no prospect of reduced dose vaccines (e.g. for smaller dogs) being registered in the near future because of the extensive (and expensive) nature of the additional experiments that would be required for such licensing."