What determines the long-term effectiveness of a viral vaccine?

[mktsgm]

TL;DR Summary

Is the rate of mutations of DNA/RNA viruses are the only or main contributing factor in developing an effective vaccine?

It is well known that RNA viruses mutate very quickly. Hence, it is said that it is very hard to develop an effective vaccine against it. With HIV and influenza RNA viruses the scientific world is still facing difficulty in developing effective long-term vaccines against them. Most influenza vaccines are very short-acting.

But Poliovirus is also an RNA virus. It seems the polio vaccines (both OPV & IPV) have been highly effective (long term) such that polio disease itself is almost eradicated.

What is different in poliovirus? Is it mutating very slowly or not at all mutating?

Is the rate of mutation only, is the main determining factor in developing an effective vaccine? Or does the immune response to the vaccines such as antibodies, T-cell response, and complement response to the type of (DNA/RNA) viruses also determine the vaccine effectiveness?

Thanks.

 

[jedishrfu]

My guess is the mutation and transmissibility factors. If it’s mutation rate is slow then a proper vaccine can stop it in its tracks in the herd. Similarly for transmissibility, if it’s hard to catch it then it resides with its host and can only mutate in the host.

 

[bhobba]

There is a mutation issue, so you are not dealing with the same disease. We see it with the flu. Then there is the actual effectiveness of the vaccine waning with time - again, we see it with the flu. Also, it seems to vary from vaccine to vaccine how many doses provides optimum protection.

Thanks
Bill

 

[mktsgm]

Thanks.

The rate of mutations would certainly impact the efficacy of a vaccine.

If structural differences like genome (DNA/RNA) do not determine the rate of mutations, I wonder what could the real reasons be?

In general, what determines the viral mutations? Are they intrinsic or extrinsic factors?

The question delves deeper...

 

[jim mcnamara]

Efficacy: Vaccines are supposed to reduce disease processes (i.e., hospital stays) and reduce fatality rates. Not prevent transmission or low level (asymptotic) responses.

So we have the media to thank for altering that perspective - in a bad way.
I'm not going to cite papers, we have been there, done that.

Influenza vaccines routinely have efficacies in 60-70% range - This is due to the large number of extant variants arising from both zoonotic (wild ducks->domestic ducks->pigs->humans) transfer of new variants and mutation in vivo with human unvaccinated populations acting as incubators. Due to lack of resistance in populations. A universal flu vaccine is being worked on.

So, if we could get a reasonable percentage of humans vaccinated with that universal vaccine then we would only have to contend with zoonosis. We did this with smallpox, Variola virus. If Covid or influenza created horrible pustules, scarring, and 25% fatality rates like smallpox, you can bet we as a world population would be 100% behind vaccination.

CDC on smallpox -- https://www.cdc.gov/smallpox/index.html

What determines long term protection:
External to patient: zoonotic control, quarantine, high vaccination rates to reduce incubator effect.

Immune system: memory Bcells, and boostering. For example, polio vaccine provides lifelong efficacy with the proper inoculation regime in children. Repeated exposure to the epitopes has an enduring effect on immune response.

 

[mktsgm]

Thanks

 

[stefan r]

Efficacy: Vaccines are supposed to reduce disease processes (i.e., hospital stays) and reduce fatality rates. Not prevent transmission or low level (asymptotic) responses.

So we have the media to thank for altering that perspective - in a bad way.
I'm not going to cite papers, we have been there, done that.

...

I think blaming the media is nonsense.

Public wants a product. There is demand for the product. Few care what term you assign.
It is fine that UPS and USPS do not pick up trash. It is not what they do. It is fine that trash collectors do not deliver our mail. Either way there is work that needs to get done

Hearing "that is not what we do" just shifts the question to "who is working on getting the job done". If no one is working on providing the product then it becomes political: "How did leadership fail us"? "Why am I getting taxed twice the global average for medical costs but still have to suffer"?

 

[jedishrfu]

It depends on where the media publishes and who listens to it @stefan r.

 

[jim mcnamara]

@stefan r - No. You are welcome to your point of view but it is biological nonsense. There are two parts to our immune system, adaptive and innate. The resistance to infection ALWAYS wanes because the innate system is a here and now system. Innate does things to get the long term aspect of adaptive to get fired up, then quits. This can be a matter of weeks. It takes months (why boosters at 6 months usually best) for adaptive to get going fully. So it will start kick in before severe disease.

And vaccines can never make up for human behavior as a primary driver for infection spread.

I'm not into debunking unscientific claims about vaccines, so consider learning about how our immune system works.

https://www.ncbi.nlm.nih.gov/books/NBK279396/

Come back and refine your comments please when you get it worked out.

And the media is the problem in a sense - you realize you are simply mimicing what they say. Complaining about vaccines and taxes does not belong in this part of the forum. Fair warning.

 

[Laroxe]

I think the way in which people understand immunity is very important, and perhaps the biggest problem is in thinking about our immune responses as a set process. We are at risk from numerous pathogens that have had to evolve a wide range of ways to exploit us as hosts. So as a species we have had to evolve a wide range of potential responses in order to defend ourselves, using these defences is both metabolically costly and potentially risky. They involve physical barriers, chemical barriers, alarm systems which activate a whole range of local and systemic responses etc and these responses are controlled in an attempt to be proportionate to the threat. This is important, because as the response ramps up the risks of "friendly fire" also increases, many of the symptoms we experience of disease are induced by our own immune system.

All of this means that to talk about what makes a good vaccine is difficult, this is because our immune system tends over time to develop specific responses to particular pathogens. One example of this is in the antibody response, there are very large differences in the persistence in the effectiveness of antibodies against different diseases. We know that antibody levels tend to fall quickly after infection or vaccination, but for some viruses that reproduce relatively slowly, have slow rates of mutations or in which the antibodies target conserved parts of the virus, very low levels might remain protective for a very long time and then allow the other memory cells to take over. Over time, our immune system develops very specific antibodies and the "best versions" that are preferentially produced.

This isn't the case with all viruses, RNA viruses in particular, (flu has some particular tricks in its arsenal) but the immune memory systems which develop over time, also remember the stages in the development of the best versions, so re-exposure, even to new variants, allows the innate immune system to go back in the history of how it developed the antibodies, it can target the epitopes on the new variants that haven't changed and build a new "best version" much more quickly.

So the first question has to be what do we expect a vaccine to do?, generally it is about prevention serious illness or death, some vaccines are very good at preventing disease but none can claim to be 100% effective in this, it always depends on the disease and various other factors.

Currently, the work on developing new vaccines, often against diseases that have resisted past efforts, is focussed on understanding the pathophysiology of particular infections and facilitating the development of the immune memory systems that offer the most protection. For this the best vaccines would need to target a wide range of epitopes, ideally these should be parts of the virus necessary for infection and highly conserved. This is the basis for the development of the so-called universal vaccines for coronaviruses and flu. It does seem that we need better information about the timing of vaccine schedules, the best long term responses take time to develop, and it's even possible that rapid over exposure can inhibit these responses. Generally, longer and repeated exposure allows the immune system to refine the antibodies it produces and the route of administration can affect the type of immune response, so nasal or oral vaccines using live vectors produce a greater response in the local tissues.

I think with Covid 19 we have seen all sorts of stories focussed on transmission, asymptomatic disease, reinfections and the degree of protection from infection, these have been the source of mass confusion and manipulation. I do believe that the media has had a significant role in this, but then so have politicians and many scientific bodies who have increasingly supported social control methods to enforce heath behaviours, often not based on science at all. Currently we have a situation in which the UK is basically dropping all restrictions while other countries are introducing mandatory vaccination and more social controls.

The primary purpose of the vaccines have always been to reduce the burden of serious disease, and in this they have been very effective. The current drive for booster doses has really been driven by the desire to prevent disease, which very high levels of antibodies will do, but for a short period time, it's certainly not a long term solution. Currently, we simply don't know how persistent the long term immune memory systems are and even this doesn't represent a single system, getting accurate information about this is more difficult and takes time.

So to get a good vaccine, first understand your pathogen, and how it causes disease, that's always the starting point. The question is really, how do we create a good vaccine against ... ?(insert disease here). Its worth checking out information on the development of a vaccine for HIV a hugely problematic and complex endeavour, which describes the very creative ways many of these issues are addressed.