The performance of vaccines is based on three fundamental factors: (1) the vaccine antigen (immunogen); (2) the host (human or animal) immune response; and (3) the pathogen (infectious or effective dose; replication rate in the host ; pathogenicity: tissues infected, immune avoidance responses, and damage to the immune system).
Before I discuss the above factors, I need to address an obvious question, “How is a veterinary microbiologist and parasitologist qualified to discuss human vaccines and those for COVID specifically?” First, of 30 plus new human pathogens, including SARS-CoV-2, detected in the last three decades, 75% came from animals. Furthermore, in addition to having a DVM, I have a PhD from a medical school in biochemistry and microbiology concerning human metabolic and infectious diseases, respectively. I am board certified in veterinary microbiology and parasitology (Diplomate of the American College of Veterinary Microbiologists, 1984, and a Charter Diplomate in Veterinary Parasitology, 2011). I have served the USAF and other agencies and Military Services of the Department of Defense in countering biological warfare for over 30 years. I was consultant to the USAF Surgeon General on Veterinary Microbiology (the last one). I retired as the USAF Senior Scientist in Chem/Bio Counterproliferation and Electromagnetic Bioeffects in 2011. And, I have advised them as a contractor from time to time in these areas ever since, including on how to neutralize SAR-CoV-2 in the air using electromagnetic radiation and how to counter biotechnological weapons.
In respect to the first factor, antigens, it is very important to select the proper one as an immunogen to induce protective immunity against initial infection and/or specific disease manifestations. Vaccines may not fully prevent infection (as with SARS-CoV-2 delta variant), but can reduce or prevent disease. However, recent evidence from Sweden and Finland show that they inhibit transmission within family units containing unvaccinated individuals as the number of family members vaccinated increase (45% to 97% lower risk of contracting COVID-19 as the number of immune family members increased). Also, mild infections have recently shown to provide strong enduring immunity which meets the Sabin Rule, “that a vaccine cannot give any better immunity than that derived from a recovered infection.” The exception is when a dysfunctional immune pathway is triggered as in “ long hauler” COVID or when non-neutralizing antibody is induced as is abundantly seen in such other infectious diseases as HIV AIDS or symptomatic progressive rabies. SARS-CoV-2 infection, especially if widespread in tissues prior to immune resolution, has a propensity for triggering a detrimental immune pathway. Also, aborted upper respiratory infections, as in children, are mitigated by innate immune responses such as those driven by interferon which truncates the development of a lasting specific immune response to COVID and can lead to re-infections as children age and become adults. The virus is in a race with the immune system to replicate, transmit and cause disease before it can be eliminated by the immune system. This principle being recognized, one must be aware that vaccine induced immunity is not absolute and can be overcome in a spectrum of infection and disease states. In countering biological warfare, those investigators, such as myself, had to be acutely aware of this fact in order to gauge effective responses to various levels of attack and exposure, from overwhelmingly massive bio weapon attacks to collateral release from destroying biological weapon production and storage facilities. Also, the route of exposure from aerosol, to skin contact, to ingestion had to be considered. I once had to answer a Special Forces General Officer Commander on why his vaccination against anthrax did not remove the necessity for other physical barrier and sanitary precautions in a massive attack or exposure scenario. To quote a Russian military proverb, “Quantity has a quality all its own”. Vaccines are meant to provide logs of protection (10-fold increases in the infectious dose) which can be overcome by very high exposures rather than absolute protection. This is why talking about percent protection of a population can be misleading. These percentages are based on an average dose of agent under ordinary circumstances. They are assuming everyone receives the same dose and just have variations in their immune responses to the infectious agent, SARS-CoV-2, specifically. Acceptable vaccines give about 2 logs of protection, good ones 3 logs and excellent ones more than 3 logs. Some of the best vaccines are against toxins and fall into the last category, such as those against diphtheria, tetanus and clostridial toxins (vaccination with inactivated toxins called toxoids). These limitations are why we need to reduce viral output within a population and within a certain exposure circumstance regardless of vaccination status. Why we need to reduce the number in a population producing large amounts of transmissible virus to stop the pandemic. Also, viruses do not mutate with intent. The mutations beneficial to their survival, replication and transmission are directly related in their probability to the amount of virus produced and circulating.
The second factor, the host immune response can become the limiting factor for any vaccine no matter how well designed and it is performing in the general population. This is why the tragic example of Colin Powell’s dying of COVID because of immunosuppression by multiple myeloma, a cancer of plasma cells that suppresses the body’s immune response, is so illustrative. Again, it demonstrates that percentages of protection are no assurance for the protection of an individual unless most of the population around that person is vaccinated. The probability of overwhelming an individual’s immune system by the virus goes down precipitously as the amount of viral exposure goes down. The measure of circulating neutralizing antibody is only one indicator of protective immunity, cell-mediated immunity is also and sometimes more important over the long term. This is carried by lymphocytes and also mediated by other immune cells such as macrophages. Another very important measure is the “immune memory” which resides in specialized lymphocytes. This anamnestic response usually occurs within 3 days. For most natural infections, this response time is sufficient, but for overwhelming exposures with agents, especially by aerosol, and/or with very low infectious doses (as with Q Fever agent, that needs only one organism to infect), the race between the immune system and the pathogen can be very close. Again vaccination is necessary, but not sufficient under circumstances of high infectious dose exposure.
The final factor to be considered here is the pathogen itself. Vaccines may prevent disease but not be able to prevent infection especially if the infectious agent can hide from antibody and immune cells in “privileged” sites such as intracellular, in the brain or kidney, gastrointestinal tract, etc. or if they attack the immune system itself as HIV does and SARS-CoV-2 does to a much more limited extent. This could potentially lead to carrier states, but these are more likely with large viral loads as in naive infections rather than lower viral loads in vaccinated individuals. For COVID, intranasal vaccines are being pursued to induce IgA, a secretory antibody, that stops and neutralizes the virus at the mucosal surface. This would prevent the possibility of widespread tissue invasion by the virus before the immune system could kick in to neutralize it, greatly decreasing the potential for damage and disease seen in the slow response of an initial immune response (2 weeks or greater). The latter is why single vaccination individuals get infected and show symptoms during the two weeks after initial vaccination. It is not a failure of the vaccine. It is just that the virus won the race. This is why mutations that lead to variants that rapidly replicate and disseminate in tissues are such a threat. Our military group addressed such rapid, low dose infecting microbes by developing small synthetic DNA which could be selected in the test tube rapidly to bind to new variants for immediate neutralization and with an additional binding site to attract antibody induced by earlier vaccines to redirect the immune system against these new “rapid variants”. We even showed it could be delivered by inhalation. All these statements are supported by my other posts and data in the references of this blog, and by experience with many other especially dangerous pathogens. The final word: No one is safe until we are all safe.
Global Biosurveillance 