Dear Dr. Rodney P Jones

On immunization, the initial detection typically is done by the innate immune system; although, B-cells may also perform this function. This detection process begins when the immune system recognizes epitopes on antigens.

Multiple components of the innate immune system will then respond to this challenge. These components of innate immunity will opsonize or bind to the agent and aid in its engulfment by antigen-presenting cells such as macrophages or monocytes. These antigen-presenting cells will then process the antigens from the pathogenic agent and insert the processed antigen along with the MHC protein onto the surface on the antigen-presenting cell.

If it is a viral antigen, the antigen will be bound with MHC I protein and presented by the antigen-presenting cell to a CD8 cell which will likely trigger cell-mediated immunity. If it is a bacterial or parasitic antigen, the antigen will be bound with MHC II protein and presented by the antigen-presenting cell to a CD4 cell which will likely trigger antibody-mediated immunity. These are a few events that may take place initially.

There are many factors that can determine how antibodies are produced by the body after a vaccine is administrated. These factors include the patient’s age, sex, genetics, and comorbidities.

For example, infants who receive the measles vaccine before the age of 9 months have significantly lower levels of antibodies, as well as much lower antibody avidity as compared to patients who received the vaccine between the ages of 9 and 12 months.

The patient’s sex can also affect vaccine response. Females, for example, have been found to have higher antibody responses to dengue, Hepatitis A and B, inactivated polio vaccine, rabies and smallpox vaccines, whereas males appear to produce higher concentrations of antibodies after receiving vaccines against tetanus, diphtheria, pneumococcal polysaccharide vaccine (PPV23), PCV7 and meningococcal conjugate vaccine (MCV-C).

There are behavioral factors that include exercise, alcohol consumption both chronic and acute psychological stress, sleep duration, nutritional status, as well as consumption of micronutrients like vitamins A, D, and E which can affect the ability of antibody production following vaccine administration. Smoking has been shown to reduce antibody production following the administration of the Hepatitis B vaccine. Comparatively, although antibody production levels are not affected by smoking after immunization for the human papillomavirus (HPV), antibody avidity can be affected.

Also, vaccine itself can determine how the patient’s immune system will respond following its administration. For instance, the vaccine schedule, site of administration, route, needle size, time of day, whether any other vaccines are administered concurrently, as well as whether the patient is also taking other drugs at the time of the immunization.

I have attached a few articles for your reference which my be helpful.

Article A guide to vaccinology: from basic principles to new developments

Article Immunological mechanisms of vaccination

Article Fundamentals of Vaccine Immunology

Hope this helps!

Regards,

Malcolm Nobre

Dear Malcolm,

Thank you very much for a very comprehensive answer.

Do you have any idea why mortality in those with a COVID-19 vaccine would be higher in the first 21 days after vaccination than in the unvaccinated?

This information is in this link: Effect of Age, Sex, and COVID-19 Vaccination History on All-Cause Mortality: Unexpected Outcomes in a Complex Biological and Social System [v1] | Preprints.org

We are working on a revision that shows the 21 day situation more clearly.

Much appreciated.

Rod

What type antibodies do you want to detect. Moreover it depend on vaccine

Dear Vardan,

I am not even sure that antibodies are the answer I am looking for. Have been scrabbling around looking for potential reasons why deaths may be higher in the vaccinated than the unvaccinated after COVID vaccination during the first 21 days after vaccination.

Regards

Rod

There is a quite well known timeline.

Depending on which adjuvant is used with the antigen, (in the covid vaccine the adjuvant is the single stranded mRNA itself, which induces a nonspecific inflamatory response leading to productive antigen presentation as described in the first answer, although it is dendritic cells and not macrophage or monocytes that typically induce a robust primary immune response) in the first 7 days the IgM isotype predominates. During this time interactions between the IgM producing B cells and Helper T cells direct the B cells to undergo isotype switching, in most cases primarily to the IgG1 isoptype. So as IgM peaks at around day 7 IgG1 levels begin to rise, peaking at around 14 days. The antigen specific B cells activated will primary produce low affinity antibodies.

After 21 days the immune system can be boosted with a much lower dose of antigen which quickly results in affinity maturation where the B cells with the highest avidity to the antigen compete for and thus present the antigen to rapidly expanded antigen specific memory T cells, whose cytokines can induce further isotype switching, for instance when exposed to T helper cells producing IFNgamma the B cells are induced to switch to the IgG2a isotype. Through both antigenic competition and affinity maturation processes the resulting antibodies during the boost response are selected to have much higher affinity for the antigen. These secondary response antibodies peak approximately 7 days after the boost.

The issue with higher mortality during the first 21 days could just be a Confounding factor, i.e., something associated temporally with the increase in deaths but which has no real impact on the mechanism or cause of the increase observed. I would think that a study with enough power, i.e., looking at a big enough sample size would find this result as it seems highly unlikely that primary immune activation would be causative of a significant increase in all cause mortality. Very Highly unlikely....

Randall

Hi Randall,

The sample was the whole of England. See attached spreadsheet which demonstrates the effect. Note that this spreadsheet is part of a revision of a submitted paper, Effect of Age, Sex, and COVID-19 Vaccination History on All-Cause Mortality: Unexpected Outcomes in a Complex Biological and Social System [v1] | Preprints.org and will itself be listed as a revised preprint v2.

Any thoughts welcome. I recall that someone else reported a similar increase in the Netherlands. I need to find that study.

Rod

I think it is a result of immune storm induced by vaccination

A very likely outcome/cause.

I think the immune system is very complex and vaccination that is considered as alternative to combat with resistance to antibiotics can has many side effects.