Vaccine Preparedness

On the 9^th November 2020 promising results from a vaccine candidate against Covid-19 were announced by Pfizer and its partner, the German company, BioNTech. They stated that their candidate vaccine (BNT162b2 (modRNA)) was “more than 90 percent effective in preventing Covid-19 in participants”.

Whilst there have been substantive funds poured into vaccine development in the UK, EU and USA, Pfizer were quick to clarify that they funded the research with their partner independent of governments’ support. In July, Pfizer negotiated a $1.95 billion deal with the US government’s Operation Warp Speed, the multiagency effort to rush a vaccine to market, to deliver 100 million doses of the vaccine. The arrangement is an advance-purchase agreement, meaning that the company will not be paid until they deliver the vaccines. Delivery itself appears to be a significant challenge as the Pfizer vaccine needs to be kept at minus 70 degrees Celsius (-94 F) or below.

A week later, the 16^th November, Moderna presented similarly promising preliminary results. Moderna recruited 30,000 volunteers across the United States to participate in its trial. A quarter of the participants are 65 years or older. White people make up 63 percent of the volunteers; 20 percent are Hispanic; 10 percent are Black; and 4 percent are Asian Americans. The United States government provided $1 billion in support for the design and testing of the Moderna vaccine and an additional $1.5 billion in exchange for 100 million doses if the vaccine proved to be safe and effective. They have proposed that theirs requires less stringent temperature controls.

Early Days

Data is thin on the duration of benefit and the effects in differing age groups and safety are a way off being clarified. Encouragingly, the Pfizer trial has not reported to date any severe “adverse events” in the 43,500 trial participants, Moderna has yet to release their findings. While most vaccine-associated severe reactions occur shortly after vaccination, it will be important that trial participants and those vaccinated following licensures are closely followed to ensure that the benefits of receiving the vaccine outweigh any risks.

Importantly, the data released by Pfizer on November the 9^th and Moderna on the 16^th were delivered in news releases, not a peer-reviewed medical journal. It is not conclusive evidence that the vaccines are safe and effective, and the initial finding of more than 90+ percent efficacy could change as the trials go on.

BioNTech and Moderna have purposed a technology that has never been approved for use in people until now. They take genetic material called messenger RNA and inject it into muscle cells, which treat it like instructions for building a protein, a protein found on the surface of the coronavirus. The proteins then modulate innate and adaptive immunogenicity and are believed to confer long-lasting protection against the virus.

Ten other vaccine makers are also conducting big Phase 3 trials, including efforts in Australia, Britain, China, India and Russia. More than 50 other candidates are in earlier stages of testing.

Phase 2 preliminary results data published in the Lancet on the 18^th November 2020 on the single blind Oxford ChAdOx1 nCov-2019 vaccine study shows that it triggers a robust immune response in healthy adults aged 56-69 and people over 70.

Whilst further data needs to be examined, it appears to be a developing narrative, that the immune system responds to at least three triggers – non vaccine expose, vaccine trigger via lipid particle mRNA generation of immunity and adenovirus-vectored vaccine which contains a pathogen-specific transgene.

ChAdOx1 nCoV-19 is a replication-defective chimpanzee adenovirus-vectored vaccine expressing the full-length SARS-CoV-2 spike glycoprotein gene (GenBank accession number MN908947).

Transparency

In a move to shore up public confidence around the novel development of the vaccine, and after criticism from outside researchers, Pfizer and other companies took the unusual step of releasing their trial blueprints, known as protocols, revealing typically secret details about how it was evaluating its vaccine. Public confidence in the drug companies’ findings and regulators rigour and independence will be critical in persuading populations to consider the merits and get vaccinated.

Pharmaceutical companies have had their reputations severely damaged due to multiple failures of policy (fraud) as well as medicines. Quite understandably there is anxiety about the proposed vaccination of billions of people. Albeit, initial >90% efficacy outcomes are likely to persuade people far more than the anticipated 40-50%.

There is precedent for a greater type of transparency. The large Recovery trial run by the University of Oxford, which helped determine that the steroid dexamethasone reduces deaths in patients with Covid-19, has published its trial protocol and statistical analysis plans, helping clinicians and the public understand the assistance it offers.

Nutrients and Immunity

What we can be relatively clear about, is that Immunity is a multifaceted phenomenon. The concept of the herd immunity threshold, which refers to the fraction of the population that needs to be immune to prevent an ongoing epidemic spread of an infection, has been a major focus of research and extensive discussion since the early days of the SARS-CoV-2 pandemic.

The herd immunity threshold is reached when an infected individual infects fewer than one other person, on average. For a novel infection for which there is no pre-existing immunity, herd immunity can be generated either through infection with the pathogen or through vaccination. The primary mechanisms for developing resistance and immune memory relies on the development of antibodies and T cells with existing viral familiarity and related cytotoxicity.

Although much remains to be understood regarding the immune response to SARS-CoV-2, and how vaccine-induced protective immunity may differ from natural immunity owing to the immune-evasion strategies of the virus, an improved understanding of the natural immune response will be instrumental in developing effective vaccine and therapeutic strategies. One of which we can easily integrate into our clinical care, namely the provision of adequate nutrients required to offer both natural and vaccine induced immune development, and safely.

Adequate and appropriate nutrition is required for all cells to function optimally and this includes the cells in the immune system. An “activated” immune system further increases the demand for energy during periods of infection, with greater basal energy expenditure during fever for example. Thus, ‘optimal nutrition’ for the best immunological outcomes should be nutrition and supplementation, which supports the functions of immune cells allowing them to initiate effective responses against pathogens but also to resolve the response rapidly when necessary and to avoid any underlying chronic inflammation.

The immune system’s demands for energy and nutrients can be met from exogenous sources i.e. the diet, or if dietary sources are inadequate, from endogenous sources such as body stores. Some micronutrients and dietary components have very specific roles in the development and maintenance of an effective immune system throughout the life course or in reducing chronic inflammation and can also be supplemented exogenously.

Healthy eating, exercise, sleep, stress management, vitamins, minerals, fatty acids, and other natural agents can help mitigate the seriousness of diseases and health conditions, and even protect and save lives. The distinction that needs to be made, though, is what good nutrition, lifestyle and supplements cannot do is to stop a virus or bacteria from infecting people but is an “essential component” of outcome determination.

Vaccine readiness

In terms of determining nutrients that confer a benefit on vaccination (including those approved for Covid-19) it is necessary to draw on prior work, as there are no current vaccines to test against. As may be expected Vit D status has an impact on tolerisation, and may be of particular importance for older people. Zinc, A and E deficiencies have been noted to diminish benefits from vaccination in younger patients. Further work shows that Vitamin C, B vitamins, Copper, Selenium, Iron, Probiotics and EFAs are all required to ensure best response patterns to infection and vaccination.

To Vaccinate or Not

The WHO recognises that vaccine hesitancy is a global challenge, and is nothing new. As we are likely to be asked to consider multiple vaccine candidates in a short time frame, this uncertainty it is going to create natural barriers to public acceptance.

Where we are presently, is that whilst there are many factors yet to be qualified regarding immune generation via a vaccine, a healthy and adequate nutrient status is a clinical benefit not a risk. If you have family or friends looking to receive a vaccine, the message is clear, there is a better outcome from efficiency and reduction of risk in those people with suitable micronutrient status than in those without.