Mechanism of Covid vaccines

[mktsgm]

TL;DR Summary

What is the mechanism/physiology in which the covid vaccines help smothering the disease progression and hospitalization?

As the Covid vaccines become more prevalent worldwide, the hospitalization and mortality rates are coming down hearteningly.

Actually, what happens after vaccination?

1) Vaccination causes the production of antibodies. So when later infection happens, the antibodies are up and ready to bind and neutralize the viruses.
2) Is antibody production, the only mechanism that prevents disease progression?

What about the other components of the immune system? How do they react, after vaccinated people are infected by SARS-CoV2? Do the following get suppressed or do they get activated in breakthrough infections?

i) The complement activation?
ii) The other cytokines?
iii) The platelet activation?

Apart from these, how do the following immune components behave after vaccination?

iv) Innate immune system reaction?
v) T-cell reactions - CD8+ and CD4+
vi) Whether th1 pathway dominates or th2 pathway dominates?

Overall, how do we compare the exact mechanisms of the total immune reactions of vaccinated and unvaccinated people?

In other words, exactly what is the mechanism/physiology in which the vaccines help smothering the disease progression and hospitalization?

Thank you,

 

[Ygggdrasil]

Here's a passage from an article on adaptive immunity to SARS-CoV-2 that has a decently good explanation:

An ideal COVID-19 vaccine would elicit long-lasting high titer neutralizing antibody titers and would provide sterilizing immunity to prevent disease and onward transmission. Even if that is not accomplished, a vaccine could still be highly effective at preventing serious COVID-19 disease. If the neutralizing antibody titers are sufficient to blunt the size of the viral inoculum, the presence of memory T cells may control the infection. The working model described above (Figure 2), with severe COVID-19 cases being associated with a failure to make a T cell response fast enough during natural infection with SARS-CoV-2, is good news for vaccines, because vaccines overcome/bypass the speed problem of adaptive immunity and T cell responses. Priming of the immune system by a vaccine happens well in advance of virus exposure. Additionally, the findings that Spike is a good target for CD4+ T cell responses, Tfh cell responses, and CD8+ T cell responses in SARS-CoV-2-infected people is good news for vaccine development (Grifoni et al., 2020; Juno et al., 2020; Rydyznski Moderbacher et al., 2020; Peng et al., 2020), because almost all COVID-19 vaccines target Spike only.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803150/ (The full article is a great reference on the immunology of SARS-CoV-2 and very much worth a read)

In other words, vaccines will primarily protect from infection through the production of neutralizing antibodies that can bind to an inactivate the SARS-CoV-2 virus. If these antibodies are not present in high enough amounts (due to waning immunity over time) or are not as effective (due to the emergence of new variants), T-cells can protect against severe disease by helping to control the infection by culling infected cells and stimulating memory B cells to make antibodies again.

Consistent with this model, new research examining the correlates of protection for SARS-CoV-2 suggests that the amounts of neutralizing antibodies correlate well with protection against infection. Note that this research does not necessarily suggest that neutralizing antibodies are the only source of protection; production of an antibody response depends on an efficient CD4+ T-cell response, so the presence of neutralizing antibodies reflects both a functioning antibody response and a functioning T-cell response. Experiments in animals suggest that both the antibody response and the T-cell response help protect against infection.

 

[mktsgm]

Thanks Ygggdrasil

That was a wonderful link you have provided. It discusses a lot more Covid information scientifically. It is a treasure of information.

 

[Laroxe]

I'm increasingly coming to the view that trying to separate out the effects of the innate / adaptive immune responses isn't very helpful, there are no clear cut-offs, our response to infection follows a flexible continuum. This ranges from fast, general defences that have low metabolic costs to the slower, more complex and costly responses. However, it's the early responses that prepare for and initiate the more costly responses, and they are costly as the restraints on our immune system are removed it is the actions of our own immune system that can be responsible for the widespread damage caused by many serious infections.

Most virus's gain entry to the body via specific routes, in the case of Covid-19 this usually is in the cells lining the upper respiratory tract. Many of the cells are equipped with receptors capable of recognising pathogens and one of the first response's to a virus entering a cell is for these cellular sensors to promote the expression of interferons (IFN) and a variety of inflammatory cytokines. These have a number of effects, one is to stimulate the expression of genes in the surrounding cells to increase the number of these sensors that increase interferon and cytokine production. This has a direct effect on the virus's ability to infect these cells and attracts the attention of more specific immune cells. These effects are dose specific, so the effects reflect the number of cells infected, but it is these signalling molecules that initiate and control the activity of the immune systems we call adaptive, the systems are interdependent. One of the first active responders to these signals are called natural killer cells which kill cells identified as infected, this prevents the virus developing, but as the level of these signals increase they become increasingly less discriminating in the cells they destroy. It may be that as the range of indicators expressed on cells, that the NK cells consider suspicious widen, as well as increased tissue damage, it may be one of the reason's that the risk of autoimmune responses also increase. While there are clearly some specific changes that occur in tissues that reflect a more targeted response to specific virus's, it's generally thought that current vaccines don't have a great effect on these. There is currently work on delivering vaccines or boosters by inhalers to increase this tissue level immunity.

I did find this review paper on the development of immunity from the infection and the vaccine, which provides lots of useful information. I actually think it might be better to consider the initial antibody response as a response to control the infection and prevent relapse, maintaining high antibody levels to prevent re-infection over time is simply inefficient. Its actually interesting that as the memory cells that do offer more persistent protection, start to increase, antibody levels fall very quickly initially, before the fall slows. It also seems based on the Israeli experience that after a 3rd vaccination at 6 months the antibody levels falls much more slowly, this may be an interesting adaptation to evidence that the threat of this disease persists. (but that is just my thoughts)

https://www.ecdc.europa.eu/en/covid-19/latest-evidence/immune-responses