What are the Correlations Between Vaccine Side Effects & Antibody Levels?

[bhobba]

It is considerably more than an arbitrary interval and best guess. These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science. Of course, biology is quite complicated, and we can't really know for sure in the absence of clinical trials that test and measure the duration of immunity.

I know you are talking about the Pfizer and Moderna vaccines predominant in the US, but the latest data suggests for the Oxford vaccine (which will be the main vaccine in many countries like Australia) the main determinant of effectiveness seems to be how much later you get the second shot. 12 weeks seems about optimum. They only found this out via a mistake - half dose first then 90 days later the second dose produced 90% protection. The main factor for the better immunity seems to be the delayed second dose. I think the effect of a half or full first dose is minimal, at least according to an article I previously posted 'Although not directly presented in the paper, it appears that with a 12-week gap between doses there was very little difference in efficacy for those receiving an initial half or full dose.'. If true we could quickly inoculate with kalf doses, then as supplies of the vaccine build up give the second full dose. Australia has been producing doses since late November so already has a reasonable stockpile.

Added later. Just a note that this was found out by pure luck. The UK went against the science and decided to vaccinate as many as possible with a first shot, delaying the second shot. Many people, including me, were appalled at this. But, lucky for Boris, this turned out to be, at least for the Oxford vaccine, the best strategy. Boris was lucky, very lucky. It's good for Aus though allowing more to be vaccinated with the first dose, leaving the second dose for 3 months when our stockpile will be even greater. If I was Boris I would not push my luck too far. This worked well, and something valuable was discovered, but the odds are it will blow up in your face next time.

Thanks
Bill

 

[Tom.G]

Just a note (coincidence?) about the Moderna vaccine.

Today three of us received the first dose of the Moderna COVID vaccine. A few hours later we all took naps, ranging from 1/2 to 2.5 hours. Two of us were one hour short of sleep to begin with.

 

[bhobba]

Just a note (coincidence?) about the Moderna vaccine. Today three of us received the first dose of the Moderna COVID vaccine. A few hours later we all took naps, ranging from 1/2 to 2.5 hours. Two of us were one hour short of sleep to begin with.

I think that fits in with the UK experience where, as I previously posted, 1/3 had a reaction, the vast majority, minor, and tiredness was one of them. I am on insulin now for my Diabetes and even that makes me a bit tired. So off for a bit of a snooze before ordering dinner. The local restaurant has these BBQ beef ribs I have become addicted to.

Thanks
Bill

 

[atyy]

It is considerably more than an arbitrary interval and best guess. These practices are based off of considerable experience gathered from work with other vaccines and reflect the best available science. Of course, biology is quite complicated, and we can't really know for sure in the absence of clinical trials that test and measure the duration of immunity.

I am really interested in a few concrete examples of this science. My complaint with medical practice is that "prevailing wisdom" just sort of grows without attribution, becomes part of the canon, and then is declared science. So far I am unaware of the data and would really like to see some. I'll bet it is pretty thin.
But if I hear one more "expert" pompously declare the initial single Pfizer shot only 60% effective I will need medication or at the least clean underwear..
And I fully agree with the desire for definitive data. But unfortunately this will not be quick. Absent a raging pandemic the delay is warranted: not so much right now. One jab, thank you very much.

Of course a trial for a delayed booster would be best. But I think the idea to vaccinate more people with the first dose, and delay the second (given supply limitations) has some backing with other vaccines. For example, for some vaccines the booster has a minimum interval, rather than a maximum interval.
https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html
https://www.immunize.org/technically-speaking/20120301.asp
"First, let’s clear up one popular misconception; there is no such thing as a "maximum interval." With very limited exceptions (e.g., oral typhoid vaccine in certain circumstances), you do NOT need to restart a vaccine series because an interval is longer than recommended. Doses given even years later than recommended are still valid because the body has “immunologic memory.” The real problem with longer than recommended intervals is not the validity of the doses or their immunologic effect. It is that, until the series is complete, the person may remain susceptible to the associated vaccine-preventable disease."

 

[bhobba]

Of course a trial for a delayed booster would be best.

I think, at least for the Oxford Vaccine, that has been done. Boris, in the UK, took a punt to give the first dose to all he can and 12 weeks for the second dose. It turned out to be the right choice, but based on the data when he made the decision it was 'risky'. The first dose still provided about 76% effectiveness which is still good. As a quote I gave previously suggested even a half dose gave good initial protection, but did not give the exact amount. I would have hesitated doing it without further data - but then again there was the big 'hint' of 90% effectiveness with a half dose and a full dose 90 days later. Considering how bad the situation is in the UK it would be very tempting to do it. These are the hard choices leaders have to make. As for Pfizer and Moderna I think it best to go with what was used in the stage 3 trials, but prioritise testing for the optimum time between doses, and optimum first dose. I suspect it is already underway, as is testing a first dose of one vaccine then a second dose of a different one.

Added Later:
It seems for the Pfizer vaccine the first dose confers 90% protection:
https://www.sciencefocus.com/news/pfizer-vaccine-single-dose-90-per-cent-effective-after-21-days/

So even for that vaccine the second dose later strategy could have value.

Thanks
Bill

 

[Ygggdrasil]

I think, at least for the Oxford Vaccine, that has been done. Boris, in the UK, took a punt to give the first dose to all he can and 12 weeks for the second dose. It turned out to be the right choice, but based on the data when he made the decision it was 'risky'. The first dose still provided about 76% effectiveness which is still good. As a quote I gave previously suggested even a half dose gave good initial protection, but did not give the exact amount. I would have hesitated doing it without further data - but then again there was the big 'hint' of 90% effectiveness with a half dose and a full dose 90 days later. Considering how bad the situation is in the UK it would be very tempting to do it. These are the hard choices leaders have to make. As for Pfiser and Moderna I think it best to go with what was used in the stage 3 trials, but prioritise testing for the optimum time between doses, and optimum first dose. I suspect it is already underway, as is testing a first dose of one vaccine then a second dose of a different one.

Here's the data from the non-peer reviewed pre-print on the Oxford-AstraZeneca vaccine:

Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268

While the data suggest a higher vaccine efficiency with >12 week delay between the first and second doses, it's worth noting that the number of individuals studies is still fairly low (thousands of participants vs tens of thousands in the phase 3 clinical trials used to provide data supporting EUA of the Pfizer-BioNTech and Moderna vaccines). The confidence intervals of the data are still quite wide and overlap between the <6 weeks and >12 weeks groups, so while the data are suggestive, collection of more data would be warranted.

The 76% effectiveness of one dose quoted in the data reflects only the period 22-90 days after vaccination. The data also seems to suggest that the protection from the single dose could wane after 90 days:

Again, the numbers for the longer time periods are quite small, so more data collection is needed to draw stronger conclusions.

A lot of these conclusions about the timing of the two doses could be specific to adenoviral vector vaccines like the Oxford-AstraZeneca and Johnson & Johnson vaccines (the Pfizer-BioNTech and Moderna vaccines are based on a different technology, mRNA vaccine technology). Because the adenoviral vector vaccines use adenoviruses to deliver the spike protein DNA into cells, there are concerns that the first dose could generate immunity to the adenoviral vector that could interfere with delivery of the second dose (and these concerns would not apply to the mRNA vaccines). See this post for more discussion: https://www.physicsforums.com/threads/coronovirus-vaccine-progress.992484/page-4#post-6454249

 

[neilparker62]

LOL.

Well, I'll be admistering those jabs in a few weeks at our local mass vaccination sites, so I'll be getting my 2nd vaccine on time.

All the best - I'm trying to think of a good slogan but the best I can come up with is: "Jabbers of the World unite!" (my sister-in-law has also joined the ranks in the UK).

 

[bhobba]

This whole thing is crazy. On one of our expert panel shows, the best known one in fact, called Q&A, last Thursday they had a discussion with immunologists etc on the vaccine. At the moment here in Aus we are churning out over 50 million doses of the Oxford Vaccine. After that we will churn out over 50 million doses of the Novavax vaccine - or buy it in - our manufacturer CSL has not decided yet - it is likely however we will make it to prevent supply problems like with the Pfizer Vaccine. We have 20 million doses (enough for 10 million people - 1/5 of our population) of the Pfizer vaccine to be rolled out at the end of the month, the Oxford in March sometime. One of these 'experts', Dr Michelle Ananda-Rajah, made the claim forget about the Oxford vaccine, and go straight to the Novavax vaccine because the Oxford vaccine only has 63% efficiency while the Novavax vaccine has 95% efficiency (from early phase 3 results). None of other 'experts' challenged her on that. I was sitting there thinking what's going on here - haven't they seen the latest data on the Oxford vaccine?

https://www.astrazeneca.com/media-c...the-primary-analysis-of-phase-iii-trials.html

One dose - 76% effective. After 12 weeks you get the second dose - 82% effective.

She has interesting views:
https://twitter.com/rajah_mich?ref_src=twsrc^google|twcamp^serp|twgr^author

Below she acknowledges the new data about efficacy, but still took it at 63% because she has some doubts about it (which seems to be the reason she didn't mention it):
https://healthcareworkersaustralia.com/2021/02/11/backing-up-our-gains/

To me the road ahead here in Aus is obvious - high priority groups get the Pfizer, we give one dose of the Oxford as fast as possible to the rest of Aus. Then the second dose 12 weeks later. It will probably take longer than 12 weeks to give the first dose to everyone - it is estimated October, so 3 months after that for everyone to get the second dose. Once the Novavax vaccine is manufactured it can then be rolled out - exactly when depending on how it interacts when already vaccinated with the Oxford or Pfizer and how long the immunity lasts - but I suspect next year sometime. Australia, being in a very good position, deliberately has decided to wait a while and get the data from other counties vaccine use before proceeding. And I think it was wise - we now know the most effective dosing for the Oxford vaccine. I am in the priority one group of 16 million so I may or may not get the Pfizer - personally though I would prefer the Oxford because I take strong precautions - leave the moderately more effective vaccine for those that may not be as carefull as I am.

But as the good doctor/immunologist correctly points out it will not get us out of trouble - many restrictions will still remain here in Aus. It will be less when the Novavax vaccine is rolled out, but I personally doubt even that will do it. I fear we are in for, an admittedly lessening, level of restrictions for a few years yet, until things get back to normal.

Added later
Actually had a reply from the good doctor to my twitter post. Her blog I posted made some valid points:

'Announcement on Feb 1 of increased efficacy by spacing two doses of the AZ vaccine at least 12 weeks apart generated some interest. This post hoc analysis of the primary clinical trial data should be interpreted with caution. Post hoc analyses aim to ask a question rather than answer one. Why? Because they rely on analysing a slice of the main trial data; have greater uncertainty around estimates because numbers analysed are usually smaller and are prone to bias which may translate to inadvertently finding patterns where there are none. This sub-study provided the rationale for the UK vaccine authority’s decision to delay the interval between vaccine doses to at least 12 weeks in order to vaccinate more people. However, a quarter of a year is a long time to wait in the middle of a pandemic. This sub-study actually raised more questions than answers (as post hoc analyses often do!). Why was the efficacy of a single dose of the AZ vaccine at preventing symptomatic infection higher than two standard doses at 76% versus 63% respectively? In other words, vaccine efficacy seemed to decline with a second dose. This trial update contained an additional 5,541 people from SA, UK and Brazil but overall vaccine efficacy with two standard doses remained unchanged from the first interim study published on Dec 8 which led to approvals in several countries (i.e. 63% among 14,379 people in this update vs 62% in the first analysis). Reassuringly, there were no hospitalisations after the second vaccine dose (n=0 with vaccination vs 15 with control). These results will reassure Britons that delaying the second dose by 12 weeks has some supportive evidence. However, for the rest of us, we keenly await the release of the AZ trial predominantly from the US with >32K people where close to one quarter will be over 65 years, due to report in the next month or so. In this large trial, people are receiving 2 standard doses 28 days apart- potentially the dosing schedule we will receive if approved, hence discussions on single dosing and delayed interval dosing of 12 weeks are largely academic for Australia.'

The statistician in me (sigh) unfortuneately agrees. There goes another 'good' idea. We can alter the timeframe of our second dose, but for some reason she seems to think the dosing schedule here is going to be 28 days. We have, lies, damned lies, and statistics or as my stats prof used to say - stats is like a bikini, it's the bits you don't see you want to know about. However trials, as detailed in my first link, are proceeding with different dosings and times between the second shot.

Thanks
Bill

 

[Jansky]

I don't know how they test it, but they can determine if your blood contains antibodies.

This is the classical method and not necessarily the way that currently antibodies and their specificity are generally tested but the basic theory applies to all antibody tests including the test strip ones. The convenient advantage/disadvantages are that it is very low-tech and quite sensitive but somewhat slow, requiring hours to overnight to analyze.

The Ouchterlony double immunodiffusion test
https://en.wikipedia.org/wiki/Ouchterlony_double_immunodiffusion

In addition and what this thread doesn't seem to recognize is that along with antibodies the second arm of the immune system the cellular immune reaction mediated by T-cells, NK(natural killer)cells, macrophages, dendritic cells and others, can have an even more long term protective and clearing effectiveness of viruses even with lowered Ab levels. And that this cellular activation is what is responsible during immunization to mediate the so called side effects of the earlier responses to the vaccination reactions through substances such as prostaglandins, leukotrienes and protein mediators such as cytokines and is quite unrelated to the slower generation of the antibodies response requiring days to weeks to fully mature.

 

[Mary Conrads Sanburn]

Last updated February 17, 2021 at 5:10 PM

[. . .]

“The CA Department of Public Health ended the Regional Stay Home Order across California. This action came as projected ICU availability rose above 15%. Counties have returned to their assigned Blueprint tiers and are urged to continue safe practices, avoiding crowds and wearing a mask when leaving home.”

[. . .]

https://covid19.ca.gov/safer-economy/

I live in California! I take Gracie Girl dog and me to parks that have now opened! Of course I love the hills in Benicia and Pt Pinole

 

[Mary Conrads Sanburn]

Covid-19 testing is required prior to my Cataract Surgery. Not looking forward for that!
All I can do is have happy thoughts. Life is a journey ~~~. I think I'm going to write some
poetry. It always relaxes me. Thank you bhobba for the tumbs up! It helped.

 

[Mary Conrads Sanburn]

I walked from home to the hospital today. I went to the lab and a nice person swabbed my nose

to test for Covid prior to my surgery.

 

[Mary Conrads Sanburn]

I had Post-Op Eye Drop Instructions after Cataract Surgery:

Ofloxacin – This is an antibiotic in order to prevent infections. One drop to the operated eye.

3 times per day (morning, noon, night) x 1 week. This drop is to be obtained from my local pharmacy with prescription.

Ketorolac – This is an anti-inflammatory medication to help the eye heal. One drop to the operated eye

3 time per day (morning, noon, night) continue drops until further instructed. This drop is to be obtained from my local pharmacy with prescription.

Week 2: KETOROLAC

2x/day (morning, night)

Week 3:

2x/day (morning, night)

Week 4:

2x/day (morning, night)

# # #

There was no pain! I am so happy to have my “healthy” left eye thanks to the surgeon and his medical staff! Of course, I thank them and those who gave me a thumbs up bhobba .

 

[bhobba]

No problrmo. Interestingly your regime after cataract surgery was exactly the same as my mother had for hers. Took a bit of time off work to help her because she had bad arthritis in the hands. I was thinking of driving her to the doctor to get it done, but he walked me through it all over the phone - it was easy-peasy.

Thanks
Bill

 

[Mary Conrads Sanburn]

Dear Bill,
You are a great son with a heart of gold!

 

[Tom.G]

Back to severity of vaccine side effects vs immunity.

Someone in Cleveland, Ohio, USA asked that question (of the local news feed?)
Short answer is "No," from Dr. Amy Ray, the director of infection prevention at MetroHealth.

https://www.cleveland.com/coronavir...us-if-you-dont-have-vaccine-side-effects.html

Cheers,
Tom

 

[Laroxe]

Summary:: Have there been any studies trying to correlate the vaccine efficacy level with the severity of the side effects experienced with each vaccination?

(Sorry if this has already been addressed in one of the other COVID-19 threads. If it has, I can delete my question or merge it into the other thread. Thanks.)

I work part-time in EMS, so I was in tier 1A for public vaccinations for COVID-19 here in Northern California. I got my first Moderna shot a few days ago, and aside from some deltoid pain, I have not experienced any other side effects. I'm active on a Medic forum (EMTLife.com), and there is a long thread there for Medics to share their experiences with each of the doses of the vaccines (many of the full-time Medics are now past their 2nd dose). The side effects vary all over the map, seemingly independent of the person's background, medical history, and level of fitness.

So since I have experienced no side effects at all, I started wondering if that might be an indicator of how my body was responding to the first vaccination shot. Does it mean that my body is ignoring it, and I'll be in the 40% of folks who get no benifit from the first vaccine? Or is it a good indicator that my body handles infection challenges well (which is my history), and is building up the antibodies without bothering to tell me about it?

It would seem that the vaccine trials would have tracked side effects from each of the immunization shots, as well as antibody levels and whether the subjects were in the 90% that were eventually protected, or in the unlucky 10% who still lost the infection battle and developed full-blown COVID-19. Are any such study correlations published? I would be very interested to see what they have found. Thanks.

I think the measures of vaccine efficiency and effectiveness, are far more reassuring than you might think. First, the measures of efficiency are calculated during the initial trials when they look at the differences in disease incidence between the vaccinated and unvaccinated. These trials use specific population groups and try to use testing to confirm disease, this can mean the figures are less useful in predicting the effects in the general population.

The most useful measures are really the ones describing vaccine effectiveness, which are taken from large population studies. These by necessity are generally less objective and need large numbers, but they provide better real world data and often use different outcome measures, these can all give different numbers. The first consideration is the rate of infection seen in an unvaccinated population, or in the placebo arm of the study, so say you have a population of 100,000 people you might see around 1% becoming ill over a 3-month period, so around 1000 cases. You then compare this number to the disease incidence in the vaccinated group over the same period, if a vaccine offered 95% protection, you would expect to see 50 cases.

You might also look at different outcomes and estimate the protection against mild disease, serious disease, hospitalisation or death. When you look at the effectiveness in this way the protection offered against serious disease or death is usually very high, often close to 100%. Few fully vaccinated people develop “full-blown” COVID-19, the real surprising thing about these vaccines is in fact, how effective they are, developers were delighted with the results.
It's rarely the case that the COVID-19 vaccine has no effect, but there are lots of things that can affect the risk of developing the disease that are not dependent on the presence of antibodies. So it's a mistake to think 40% of people get no benefit, in fact the first vaccination is by far the most important, it's that the activates a wide range of immune responses, and this takes at least 3 weeks to get established, the second dose “boosts” these responses. So far there is no real evidence of one vaccine being better than others, there are to many other things to consider, a major one being the gap between the two doses, a longer gap might be better.

 

[bhobba]

When you look at the effectiveness in this way the protection offered against serious disease or death is usually very high, often close to 100%.

I think it is 100% or very close for all vaccines. I can't even recall one serious case being reported when vaccinated. Even in India, I saw an interview with a doctor. With the new highly contagious variant over there, if one of the small percentage vaccinated got it, it never developed into a serious case in his experience.

Thanks
Bill

 

[Ygggdrasil]

I think it is 100% or very close for all vaccines. I can't even recall one serious case being reported when vaccinated. Even in India, I saw an interview with a doctor. With the new highly contagious variant over there, if one of the small percentage vaccinated got it, it never developed into a serious case in his experience.

The US CDC reports 594 hospitalizations and 112 deaths related to COVID-19 among vaccinated individuals (https://www.cdc.gov/vaccines/covid-19/health-departments/past-breakthrough-data.html). Of course, these numbers are very small given that >100 million people in the US have been fully vaccinated and the rates of hospitalization and deaths among the unvaccinated are much higher.

 

[bhobba]

Of course, these numbers are very small given that >100 million people in the US have been fully vaccinated and the rates of hospitalization and deaths among the unvaccinated are much higher.

Drats - looks like it close to 100% effective - not actually 100% effective. Maybe that's why there is a push here in Aus for once everyone is vaccinated (or at least offered a vaccine) to fully open up the economy again - even before mid-2022, the government has announced. Our vaccination rate is increasing fast - I am booked in for Monday at 3.15. The exact words used were it will then be like the Flu, which we already put up with. I hope they mean when vaccinated against the flu. This year because I am now over 75, I got the extra-strong flu vaccine version.

Thanks
Bill

 

[Laroxe]

The US CDC reports 594 hospitalizations and 112 deaths related to COVID-19 among vaccinated individuals (https://www.cdc.gov/vaccines/covid-19/health-departments/past-breakthrough-data.html). Of course, these numbers are very small given that >100 million people in the US have been fully vaccinated and the rates of hospitalization and deaths among the unvaccinated are much higher.

In some ways this takes us back to some of the original arguments about mortality data. The people most likely to die are the very old with comorbidities and this appears to be particularly true if people become seriously ill with Covid 19 following vaccination. I also noticed how many studies appeared to exclude healthcare staff who appear at particular risk due to the potentially high inoculum.
This is a large observational study of the effects of a single dose
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00677-2/fulltext

 

[fresh_42]

Scientists in Germany claim to have cracked the cause of the rare blood clots linked to the Oxford/AstraZeneca and Johnson & Johnson Coronavirus vaccines and believe the jabs could be tweaked to stop the reaction happening altogether.

https://www.ft.com/content/f76eb802-ec05-4461-9956-b250115d0577

Abstract​

During the last months many countries have started the immunization of millions of people by using vector-based vaccines. Unfortunately, severe side effects became overt during these vaccination campaigns: cerebral venous sinus thromboses (CVST), absolutely rare under normal life conditions, were found as a severe side effect that occurred 4-14 days after first vaccinations. Besides CVST, Splanchnic Vein Thrombosis (SVT) was also observed. This type of adverse event has not been observed in the clinical studies of AstraZeneca, and therefore led immediately to a halt in vaccinations in several european countries. These events were mostly associated with thrombocytopenia, and thus, similar to the well-known Heparin-induced thrombocytopenia (HIT). Meanwhile, scientists have proposed a mechanism to explain this vaccine-induced thrombocytopenia. However, they do not provide a satisfactory explanation for the late thromboembolic events. Here, we present data that may explain these severe side effects which have been attributed to adenoviral vaccines. According to our results, transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels. In analogy to the thromboembolic events caused by Spike protein encoded by the SARS-CoV-2 virus, we termed the underlying disease mechanism the “Vaccine-Induced Covid-19 Mimicry” syndrome (VIC19M syndrome).

https://www.researchsquare.com/article/rs-558954/v1

There has been a news report here, that J&J has already contacted the researchers in order to get rid of what seems to be some sort of contamination with human proteins due to the production process.

I was surprised that they reacted so quickly, but the second thought was: whatever they do to support the research group is probably the cheapest they can do at all.