(Above, inset: l-r): Dr Ben Neuman, Ph. D, Chief virologist at the Global Health Research Complex at Texas A&M University; and Dr Monica Gandhi, MD, MPH, Professor of Medicine, UC San Francisco’s School of Medicine. (Siliconeer/EMS)

 

Taking on the question – Should we or should we not get a booster also known as the third shot – public health experts are divided about who should get the third shot, and when. Currently only those who took the Pfizer vaccine for their first two shots are eligible for a third shot. Boosters are not yet available for people who got the two dose Moderna vaccine, or the single shot Johnson & Johnson vaccine, except in a few special cases (at the time of writing this article).

At a briefing by Ethnic Media Services, Oct. 1, two medical experts – Dr Ben Neuman, Ph. D, Chief virologist at the Global Health Research Complex at Texas A&M University; and Dr Monica Gandhi, MD, MPH, Professor of Medicine, UC San Francisco’s School of Medicine – offer their views.

Responding to Dr Gandhi’s op-ed in the Wall Street Journal published Oct. 1, Dr Neuman said, “The important thing to remember is that we do not know what is and is not possible and you will frequently hear people say that SARS Coronavirus 2 is endemic. It is impossible to eradicate it… Here are the reasons SARS Coronavirus 2 will probably always kill a percentage of the people that it infects: Looking at the numbers from around the world in the early phase when testing is erratic, you see quite a bit of variety. But the case fatality rate, which is the number of people who die versus the number of people who are confirmed infected, always seems to settle down to about two percent. We know there are differences with age but one out of 50 people who get COVID 19, are most likely to die, based on all the data we have now.

“There really isn’t any counter data suggesting that the virus will change to suit us. A percentage of people who are vaccinated and get breakthrough COVID, will also be hospitalized or die from COVID, and as far as we can tell this will continue indefinitely. There is no data to suggest otherwise.

Dr Neuman explains that, data suggests that using the term ‘fully-vaccinated’ is incorrect. No one is ‘fully-vaccinated’ and we do not really know at this stage what fully vaccinated would look like. What we have evidence for is waning immunity, and there are different degrees. This is where people differ in general. There seem to be two schools of thought, one that is the extreme consequentialist school, where if a person does not die then the outcome is essentially less meaningful; and the other, trying to look one step ahead mentality, as time passes after vaccination, we see that the amount of protection decreases to around 50 after five months in the data that’s presented but the amount of protection against death remains constant at somewhere around 90 percent.

This is the dichotomy that is catching people because SARS Coronavirus 2 is fundamentally a moving target. It is evolving and it is changing, and if we look at the path of change, the virus has got faster, and better at reproducing, very consistently, throughout the outbreak.

We do not have any evidence to suggest that this will be otherwise in the future. There are many variants now, but over 99 of the variants, that are infecting people currently, as of September (2021), are delta and there are now over 40 subtypes of delta out there that are being monitored.

The good news is that the effectiveness of the vaccines against delta is about the same as the effectiveness against any of the other variants. The difference is slight, at most five percent, although it does decrease at about the same rate as protection decreases against any other variant.

According to the FDA documents, there’s a relatively small difference between people who are over 65 and people who are under 65 in terms of how effective the vaccines are. It has also been seen that the benefit of a booster is very large regardless of age group.

With a booster, people end up with between five times and ten times as much antibody as they had at the peak after the second vaccine, and they end up with as much as fifty times as much vaccine as much antibody as they had right before the booster. The benefits appear to be universal, while the consequences appear to be relatively similar, across age groups.

“On that basis, it is hard for me as a virologist, to understand the FDA’s decision to recommend boosters only for a certain age group, and not for everyone, based purely on the data it would look as though universal vaccination, universal boosters, are going to be beneficial. As for the concept of a booster itself, there are very few vaccines of all the ones that we take where we only take two doses. Hepatitis A, and MMR vaccine are two of these kinds. All the other vaccines we take, generally have three or more doses of these, and we do this because we are trying to move toward a position where vaccine immunity is –

  • durable enough that you don’t have to pay extra attention,
  • durable enough that it will last for years or a lifetime.

“With additional vaccine doses, we are essentially trying to move from what is considered reasonable protection to a position of certainty, and the benefit there is very, very large psychologically, in terms of hope, and the possibility for a better life without COVID 19,” said Dr Neuman.

Dr. Gandhi started with a crash course about the immune system.
“The concept of endemicity and the concept of what makes a virus, what are the features of a virus that makes it eradicable versus sort of being able to be controlled.

To be eradicated, to have no presence on the planet essentially, except in a in a test tube, there are four distinctive features of a virus that allow that to happen:

  • no animal reservoir
  • very clear features
  • a very short period of infectiousness and then immunity for life
  • a highly effective vaccine

All of the above conditions were met for Smallpox and allowed it to leave the earth. It’s in a couple of test tubes but the features of SARS-Cov-2, COVID 19, Measles, Pertussis (Whooping Cough) – these are all infections that have animal hosts. COVID 19 infection looks like a lot of other infections – a respiratory infection, it can be spread even before you’re sick so it doesn’t have a short period of infectiousness and what we’re talking about today, we don’t know if you’re immune for life, but we do have a highly effective vaccine. What will likely happen with COVID is it will go the way of Measles, or Pertussis. It will always be with us. It’s called endemic because it’s not causing undue disease, but how do we get an infection to get to endemicity, to get to endemic, so that’s kind of a start for when I go into the immune system,” explained Dr Gandhi.

Dr Gandhi gave an outline of the vaccines that are currently available, and how each of them work on the virus.

“If done right, the vaccine should actually raise t-cells which go into your memory and then they fight viruses in a very durable way, and if they’re in your memory they can last a very long time. There’s evidence from the SARS pandemic from 2002-2003 that people who survived that still have very strong t-cell immunity after 20 years. 17 years later we have evidence from measles vaccines, that we got as a child, that we have t-cells, 34 years later and counting, and then the vaccines also raise b-cells, which if we’re lucky again, they should go into their memory bank, and then those memory banks of b-cells, they make antibodies when you need them. So importantly antibodies are going to come down with time. That’s totally normal. In fact, if we had every antibody of every cold or vaccine we’ve ever had, our blood would be so thick, we couldn’t move. So, antibodies are going to go down, but the memory b-cells become the blueprint to make more antibodies if needed, and that is tremendously important when we think about the durability of the vaccines.

“There are now several studies that show us that after two mRNA vaccines you get very strong b-cell formation in your memory, b-cell formation in biopsy lymph nodes. These are the terminal centers where b-cells are formed. In immunocompromised, those b-cells are not formed as strongly after two doses, but in immunocompetent individuals, very strong production of memory b-cells (takes place) and we have plenty of evidence including from the phase one (and) two trials, the vaccines generate strong memory b-, and t-cell of community.”

“T-cells are what modulates our protection against severe disease. We knew this even before the vaccines that people, who mounted a strong t-cell response, could have asymptomatic infection and this is true of multiple diseases. T-cells are really there to protect you from severe disease. We know that of course the vaccines produce strong t-cell immunity because in the phase one and two trials of the vaccines they didn’t just measure antibodies, (but) because we are now in the year 2020, we have the capability of measuring t-cell immunity which is actually very difficult to measure, and wasn’t measured in a lot of other trials, before of older vaccines. We have the technology now, so there was strong t-cell immunity formed to all the vaccines in just when they were being initially tested in phase one two trials. That was for all three of the ones that we have in this country, along with antibodies, and in fact, the clinical trials were very consistent. They really had high protection against severe disease in the phase three clinical trials.

“Will these vaccines work against the variants and should they continue to have activity against severe disease? If we just think about t-cells, which are not actually separated from b-cells either, the answer is yes.

“Vaccine effectiveness is not just t-cell immunity, and it’s not just the vaccine, it has a lot to do with who you are as a host, so you would need to produce that strong b-cell immunity to actually develop antibodies. If you see the virus, again it also depends on how much circulating virus there is, when there is a lot of circulating virus, even with a polio vaccine we saw breakthrough infections because when you don’t see infections among the vaccinated is when you’ve tamped down transmission in the world, usually to lower levels, and we have very high rates of transmission across this planet. It also depends on the type of vaccine, and how you give the vaccine. If you give it with a three-week duration, or four-week duration, or eight weeks between doses, 12 weeks between doses. It matters, the duration of time that you have between doses, which is why the UK and Canada likely chose the right strategy of extending time between the doses of the physio-vaccine. A good example of some U.S. data that even into the delta variant, (there is) still very high protection against hospitalizations. You’re 20 times to 29 times more likely to be hospitalized in the delta variant if you were unvaccinated, than if you were vaccinated.

“I think there’s more symptomatic breakthroughs at this time not just because of the high viral load of the delta variant but that our antibodies will decrease. It’s absolutely natural and not a glitch. It’s what happens, and it’s important to say that a Mayo Clinic study showed that there were fewer reinfections even with mild infections with the Moderna vaccine which is given four weeks apart, and is also a higher dose than the Pfizer vaccine which is given three weeks apart,” explained Dr Gandhi.

Who needs an additional booster?

“I mean no compromise patients have always needed additional boosters. They have always needed third or more shots, than even a typical three dose vaccine.

I think that vaccinating and giving a third booster to those over 65, to those who are fully, who are immunocompromised, and to selected groups for example those who are having frequent exposures (such as) a healthcare worker, who is intubating patients with COVID, a respiratory therapist, because there’s frequent exposure, and with having a lot of virus around you, you’re more likely to get infected and even have a breakthrough. It is amazing what a two-dose vaccine does in terms of storage of memory b-cells storage and memory t-cells and that’s why I think the selected booster strategy makes sense,” said Dr Gandhi.

On a question about the mandatory vaccination in schools, quote “following the full FDA approval,” announcement by California Governor Gavin Newsom, Dr Neuman agreed, “I would say I am in favor of a school age vaccination anywhere simply from the perspective of shrinking the potential reservoir for circulating COVID as much as possible. Right now 14.6 (percent of the U.S. is under the age of 12, and that is a big chunk of the herd if we’re ever going to move toward herd immunity.”