We are now several months into the vaccination campaign, and it is clear to us from our own SARS-CoV-2 antibody and immunization testing that the track record of the vaccines is very disappointing, with more side-effects than originally expected. We therefore intend to have a personalized vaccine combination in place for 2022.
It is the opinion of Doctor Robert Hess that ultimately it is clinical and biochemical data determining success rather than the phase 3 results quoted by the manufacturers, which are derived solely from empirical data. A gradual decline in immune status is to be expected, and this is also clearly evident from our retests. Here, the prognosis varies depending on the individual client and the vaccine regimen, but the basic tendency is towards a more rapid decline than that forecast by the vaccine manufacturers and the regulatory authorities. Autoimmune reactions are clearly apparent in the results of retests performed on our Premium clients.
Dr. Hess expected this, but not quite so soon. In the long term (i.e. over the next few years), he expects to see a veritable tsunami of autoimmune reactions, with a corresponding sharp increase in pathologies, ranging from allergies to multiple sclerosis. Furthermore it is to be expectedt that most of these side-effects will not be associated with the vaccines, because they will tend to manifest themselves as complex syndromes. And so we will be including more autoimmunological components in our retests to spot these conditions at an early stage. All vaccines, whether they are vector-based, mRNA-based or protein-based, elicit a very strong immune response. For example, a SARS-CoV-2 vaccine is up to 100 times more powerful than an influenza vaccine in terms of immune response. The likelihood of creating autoimmune side-effects is therefore correspondingly higher.
There are the direct side-effects of vaccination that are already known and which has been reported on several times before, especially those cases of thrombosis that can be directly attributed to vaccination and which generally occur with a vector-based vaccine. But in addition to these, we can already see autoimmune reactions associated with the mRNA-based vaccines. On the issue of myocarditis in people who have received the mRNA vaccine, we do indeed see a correlation manifesting itself. Here too, it is difficult to obtain specific figures because the resulting myocarditis does not trigger any immediate symptoms and initially goes unnoticed. This makes it very difficult to come up with any reliable statistics, and in any case, the diagnosis is highly complex.
Some time ago, Dr Robert Hess indicated that he would be extending the Standard Panel of Salvagene in this regard so as to avoid the need for the Premium clients to undergo a biopsy. Myocarditis is a condition that mainly affects men, especially in the younger age bracket. He believes that the very high levels of antibodies produced by the mRNA vaccines cause the body to overreact. The immune proteins can target the heart muscle cells in a similar way to viral infections and lead to inflammation. In our Covid-19 Immunization Program and retests, we will therefore have two clear focuses – firstly, to monitor overall immunization status, and secondly, to track and/or detect at an early stage the most significant long-term side-effects of vaccination.
For various reasons, we have to assume that the entire SARS-CoV-2 situation will persist in the long term. In particular, we share the opinion of our colleague Young Yang Gu regarding herd immunity. Doctor Hess will upload a separate podcast on this topic shortly. He can already state in advance that he does not consider world-wide herd immunity to be an achievable goal. The limited level of success, which is clearly demonstrated by the results of our retests, can be seen in the country with the most advanced vaccination program. In the UK, a successful vaccination campaign is underway, with 77% of the adult population already having received at least one jab, including 54% who have had two. On this basis, the government has now begun to cautiously open up the economy as the summer approaches, but it is in the face of a strong upward trend in infection rates, due of course to new mutant forms of the virus. This is just a foretaste of the complications that mutations will cause in the coming weeks and months of summer and beyond. In the race between mutations and vaccine developments, the virus still seems to have the edge.
While waiting for researchers at CureVac, the University of Texas and other centers to develop AI-based vaccines to mitigate the pandemic, a further option is to combine vaccines. There are approximately 25 such projects currently underway, the most prominent of which is Com‑CoV in the UK, and they are all pursuing similar leads. The current thinking is that mix-and-match brings advantages as well as disadvantages. A straightforward combination, which is the current favorite, delivers certain benefits, but also entails huge risks, because each individual has a completely different starting point. Some need a much higher T-cell immunity, while others need much greater and more effective antibody production.
The circumstances of every individual are different. The big worry is the ease with which SARS-CoV-2 can produce escape mutants and also combine its well-disguised evasion of antibodies with increased transmissibility. One example is the delta mutant, B.1.617.2, which originated in India and is responsible for the exponential growth of infection in the UK. It significantly raises the number of already existing loopholes for infection in vaccinated people. Such viruses continue to evolve in vaccinated individuals and learn to overcome vaccine protection even better. He has already stressed in previous Keynotes that the vaccinated are the very group that should be tested the most and whose results should be submitted for gene sequencing. The big risk is that no country in the world currently has the capacity to carry this out. Nevertheless, the vaccines that have been developed so far have the potential to control this infection in the long term. Each vaccine leaves gaps yet also has its particular advantages.
The question is, how can these strengths be intelligently combined to enhance their effect and provide better protection? These are the theoretical considerations behind one of the projects that Dr. Robert Hess is pursuing with his partners. One thing is certain – there is no perfect combination regimen, because the disadvantages clearly outweigh the advantages. In the adaptive part of the immune system, there are two pathways to combating the pathogen. In the so-called B-cell response, the immune cells form antibodies according to structures found on the surface of the pathogens. Well-matched antibodies bind to these antigens (e.g. viral proteins), thus rendering them blind and unable to function. Viruses wrapped in a sticky antibody film can no longer penetrate the host cells. Precise though this system may be, it is also vulnerable. Because antibodies have to latch on to the surface features in order to become attached, any change to a building block at a site favored by a certain set of antibodies can render this group ineffective. Although dozens of antibody clones form against the virus spike protein replicated in the vaccine, some mutations change the shape of the protein to such an extent that the antibodies are no longer able to bind to it. For example, in a laboratory experiment with the new beta (South African) variant, seven out of ten antibody groups failed. And this is precisely what was discovered in the SARS-CoV-2 antibody monitoring conducted with the Premium clients of Salvagene.
In some cases, the class 3 antibodies, which are classified as low-potency, are dominant, while the high-potency ones accounted for only a few percent of the total. The second pathway of the immune response is the T-cells. These are the focus of our immunization strategy, because this is where each of us has the greatest scope for optimization. Dr. Hess would therefore urge all Premium clients to rigorously implement the list of immunization to-dos. We estimate that at least 60% of all immunization lies in our own hands, regardless of whether we are vaccinated or not. The T-cells take a little longer to spring into action, but then proceed even more combatively, hurling themselves into the melee with molecular poison darts and other weaponry – immune cell against invader. The T-cells are the defense that gives long-term protection against viruses, and that is why they are the main focus of our Immunization Program. We measure overall T-cell immunity levels at regular three-monthly intervals. The T-cells orientate themselves to the surface molecules of the pathogens and are not concerned with fine details but rather with coarser general characteristics.
For recognition purposes, T-cells need only a small part of the picture where mutations are less likely. Moreover, these snippets are often located in regions that change comparatively rarely. So far, these have been consistent with the wild-type coronavirus and its current mutants. Which is why those who have been vaccinated can still become infected with escape mutants, but do not become seriously ill. As already reported, there are advantages and disadvantages to the different vaccine platforms: vector vaccines stimulate the production of more T-cells, while mRNA-based vaccines produce more antibodies. For the sort of person who does little to boost their own T-cell immunity, combining the two types makes sense. Individuals who have received a vector-based vaccine characteristically have a lower antibody count and the antibodies that they do have can be bypassed relatively easily by the virus. On the other hand, the T-cell response is strong, though this comes with the risk of an exaggerated response in younger people, especially women. In contrast, the mRNA vaccines produce a more effective antibody response that is also stable against mutants. The response in the T-cell system, on the other hand, may be weaker. A direct comparison of the two main vaccines carried out as part of a study in the UK showed that only half as many people vaccinated with BioNTech had produced T-cells capable of neutralizing the virus spike protein compared with those who had received the AstraZeneca vaccine. The findings that vaccination with AstraZeneca produces a stronger T-cell response may be due to the fact that the properties of two viruses are combined, namely the proteins of SARS-CoV-2 with those of the adenovirus which serves as a sort of taxi.
Adenoviruses are even capable of penetrating into the cell nucleus, which should be a cause for great alarm. There are various studies on this, including one at Harvard, that suggest the provision of learning templates with different pathogens significantly improves immune response. The Harvard study covered 74,000 Covid patients who had already received either a combined measles, mumps and rubella vaccine or a combined diphtheria and whooping cough vaccine. These individuals exhibited superior immune levels to members of the control group. Research done in Spain showed that Covid patients who had pneumococcal vaccination were significantly more immune. As early as last autumn, we were recommending that pneumococcal vaccines should be administered, followed up by booster jabs. With all these studies looking at combined vaccines, not a single one has concerned itself with escape mutants. Consequently, great caution must be exercised. Results so far suggest that there are definitely vaccine combinations that are significantly better than the single-variety regimens. But it is already becoming apparent that there are combinations that are less effective or in which the immune response is actually slowed down. Regarding the combinations with protein-based vaccines, Dr. Robert Hess has taken an especially close look at the combination of mRNA-based vaccines with protein-based vaccines, specifically with Novavax. Here, the spike proteins of the virus are given an effect enhancer. In addition, the proteins are highly concentrated and biotechnically modified so that our immune system has the opportunity to study them at its leisure and build even more suitable antibodies. It is theoretically possible that this might have a significant potentiating effect on the antibody system. However, the combination no longer works if a purely mRNA-based vaccine has already been given first, because the antibody reaction is then already so strong as to render the protein vaccine ineffective. When the reverse order applies, i.e. the protein-based vaccine is administered first followed by a vector-based or mRNA vaccine, the studies showed a clearly potentiated antibody formation with an across-the-board T-cell response. This results in a significant mutant-resistant degree of immunization. It is already becoming apparent that there will be a multiplicity of vaccine combinations offering many different possibilities in the coming months. But at the same time, they will entail big problems and big risks.
Against this background, Doctor Robert Hess is working to develop a customized vaccine combination for his Premium clients, which logically still cannot be 100% perfect. This was also the reason why he delayed such a long time before making any recommendations to his Premium clients while the vaccination campaign was only just starting up. He wanted to keep the options open, and from his perspective, this approach has been vindicated.
However, in the case of a booster in a few months, the question will arise: What is the next step? We assume that the amount of inoculant, i.e. the quantity delivered via the vaccine itself, will also play a role due to the current immunization status. This will naturally entail in‑depth consultation.
With so many people wanting to be vaccinated at the same time, the immune response is already being pre‑formed in such a way that certain combinations will not work. The worst case imaginable would be that the version of the virus encountered first so strongly imprints the immune system that it is no longer able to switch over when it encounters another, more dangerous version of the pathogen. We are already investigating scenarios in which antibodies are produced that actually give the infection a helping hand. The phenomenon of “original antigenic sin” (also known as antigenic imprinting or the Hoskins effect) is known to us from other infections, for example dengue fever. There are different dengue viruses – so-called zero-types – which can trigger dengue fever. After a first infection with one zero-type, people can often become more severely ill with a second infection triggered by a different zero-type, because their immune system calls up the old immune response to the original virus, but struggles to adapt to the new one.
In the case of the novel coronavirus, it is still not clear whether the immune system is sluggish in relearning or whether it reacts with some degree of flexibility. This is an issue we addressed back in April 2020. It will definitely become clearer in the next few weeks as new mutants appear and the vaccination campaign forges ahead. There is an initial study by Moderna, the findings of which have been somewhat contradictory. Some vaccinated people have already received a third dose based on the blueprints of the original Wuhan virus and the so-called South African mutant, but the results are inconclusive as to what the scope for adaptation might actually look like.
In conclusion, Dr. Robert Hess believes that, although the vaccines provide a certain platform for a solution and it was not entirely unjustified that the lion’s share of investment went into them, they will not ultimately lead to a resolution of the problem. We should therefore consider going down the second more broadly based route of antivirals, and there are already many promising projects in this regard. In the next Keynote we will look at these in a bit more detail.
As for the long-term prospects, we believe that this approach, alongside vaccines with their concomitant risks, will produce a manageable solution with very few side-effects and a significantly greater acceptance among the general population.