In case you missed it, Dr. Karen Becker interviewed Hemopet’s very own Dr. Jean Dodds about the Rabies Challenge Fund study. (You can find the video at the bottom of this page.) We thought we should address a few questions that may come up. In this post we will address immune memory cells, recombinant vaccines and sterilizing immunity.
Of course, the two doctors also discussed a range of other topics. So, we will expand on rabbit hemorrhagic disease and oxidative stress in subsequent posts.
Immune Memory Cells
The Rabies Challenge Fund (RCF) study’s team was comprised of Dr. Jean Dodds, Dr. Ronald Schultz and his associate Dr. Laurie Larson, and Kris Christine. The team measured the antibodies IgM and IgG to assess the immunity levels of the dogs in the study. This type of test is called an antibody titer test.
Antibody titer testing is a standard predictor of protection against viruses and other microbial diseases, and has been around for decades. The U.S. Centers for Disease Control and Prevention (CDC) recognizes an acceptable titer level of protection at 0.1 IU/mL against rabies infection within the USA. The World Health Organization (WHO) recognizes 0.5 IU/mL as an acceptable titer level of protection for export outside the USA.
Immune memory cells are the lymphocyte B-cells (bursal-derived) and T-cells (thymus-derived). You can think of them as military generals. They have seen things, remember them, and prepare the troops for future battles against the same virus.
What happens is that T-cells stimulate B-cells to produce antibodies like IgG and IgM. When antibodies start to wane, it is good to know if the B-cells – which are then responsible for producing antibodies – still recognize a disease and can activate a neutralizing antibody response to it.
The research team also measured B-cells during the third phase of the study.
Immune memory cell testing is a relatively new analysis, predicts immunity more specifically, but is costlier, and generally reserved for research. The current COVID-19 pandemic has been good for advancements in diagnostics as T-cell testing is now reaching clinicians.
Currently, the canine rabies vaccines available on the market are killed vaccines that contain adjuvants except for the new rabies vaccine for cats discussed below. Killed vaccines use an inactivated or “dead” form of the virus (previously live microorganisms that have been killed with chemicals or heat), along with an adjuvant (a substance which enhances the body’s immune response to an antigen) such as aluminum or thimerosal (mercury).
Companion cat parents have more options such as a recombinant rabies vaccine. It is best to think of “recombinant” as simply a descriptor of how a vaccine is manufactured. It is the complex process of recombining. So, while you might read “recombinant vaccines”, the phrase refers more to the vaccine technology rather than the vaccine.
Recombinant vaccines rely on the capacity of one or more antigens to induce immunity against a pathogen, whether administered with adjuvants or when expressed by harmless bacterial/viral vectors or plasmids.
The feline recombinant vaccine uses a viral vector called canarypox virus (CPV), which works by expressing gene products in the absence of productive viral replication. Since CPV is a bird pathogen, recombinant canarypox vectors infect but do not replicate in cats.
The RCF research team divided the dogs with less than 0.5 IU/mL titer antibody test results into four groups:
Group A – previously vaccinated six years and one month prior to booster, boosted with killed rabies vaccine.
Group B – previously vaccinated six years and one month prior to booster, boosted with recombinant rabies vaccine.
Group C – naïve (never had a rabies vaccine before), vaccinated with killed rabies vaccine.
Group D – naïve (never had a rabies vaccine before), vaccinated with recombinant rabies vaccine.
By the 14th day after re-vaccination, 90% of the previously vaccinated groups showed antibody responses at or above 0.5 IU/mL, compared to 30% of the naïve dogs. Furthermore, the recombinant rabies product licensed for cats induced anamnestic responses (denoting an enhanced reaction of the body’s immune system to an antigen that is related to an antigen previously encountered) several-fold higher than the killed virus product when given to previously vaccinated dogs. The same recombinant product did not induce any naïve dog to respond above 0.5 IU/mL by study day 14.
Remember: we knew that immune memory was present based on testing and the recombinant vaccine demonstrated this by safely eliciting an immune response as indicated by the antibody titer test and immune memory test.
However, we need everyone to follow the law when it comes to rabies vaccines. Rabies is a very dangerous, fatal and transmissible disease for all mammals including ourselves. So, do not go seeking out the recombinant feline rabies vaccine to be used on your dog. You will need to wait until a recombinant canine rabies vaccine is approved.
Dr. Dodds mentions that we know that feline panleukopenia, canine distemper, infectious canine hepatitis (canine adenovirus-1), and canine parvovirus all produce sterilizing (lifelong) immunity. This is when a companion cat or dog is infected with one of these viruses and survives. The vaccines against these viruses produce the same effects, if given at the right times.
Why don’t we know if rabies produces sterilizing immunity? Because this and other types of viruses differ, and further specific research addressing the point has not been done.
Again, rabies is fatal disease. As of June 2019, less than 20 cases of human survival from clinical rabies have been documented, and only a few of these survivors did not have any pre- or postexposure prophylaxis (action taken to prevent disease, especially by specified means or against a specified disease) history, according to the CDC.