Sept. 29, 2020 -- An experimental vaccine against the virus that causes COVID-19 appears to generate more antibodies in people over the age of 70 than it does in even middle-aged adults.

If the antibody responses seen in the study translate into protection against the infection, the results could mean the elderly -- the population that has been hardest hit by COVID -- could receive strong protection from the shot. According to the CDC, eight out of 10 COVID-19 deaths in the U.S. have been in adults over age 65.

The vaccine, mRNA-1273, is made by the drug company Moderna, and it uses a new type of technology to coax the body to produce an immune response to the virus.

Basically, instructions for making the spike protein on the new coronavirus are injected into the body, where they are taken up by our cells. Cells then use those instructions to make the protein, which is released by the cells and recognized by the immune system. The immune system then makes weapons -- including antibodies -- against it. The hope is that when the real virus comes along, our bodies will have a jump-start and be ready to fight.

The study was small, with just 10 people included in each group, for a total of 40 people in the study. Results from the phase I trial of the vaccine show that adults over the age of 70 made roughly 3 times as many antibodies after their second dose, compared to adults ages 56 to 70.

“This is surprising because it has traditionally been observed that vaccine responses wane with age. Stated another way, antibody responses are usually lower with older age,” says Wilbur Chen, MD, who specializes in vaccine development in older adults at the University of Maryland. He was not involved in the study.

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Coronavirus in Context: Vaccine Regulations and Pharma's Safety PledgeWebMD's Chief Medical Officer, John Whyte, speaks with Richard Moscicki, MD, Chief Medical Officer, PhRMA about Vaccine regulations and Pharma's safety pledge.1023

[MUSIC PLAYING]

JOHN WHYTE: You're watching

Coronavirus in Context.

I'm Dr. John Whyte, Chief

Medical Officer at WebMD.

Vaccines certainly are

in the news.

Vaccine safety is concern

for many people.



To help provide some insights

into vaccine development,

I've asked Dr. Richard Moscicki,

he's the Chief Medical Officer

of the Pharmaceutical

Researchers and Manufacturers

of America and a former Deputy

Center Director at the US Food

and Drug Administration.

Dr. Moscicki thanks for joining

me.



RICHARD MOSCICKI:

A real pleasure, John.



JOHN WHYTE: Let's talk

about this pledge

that the vaccine manufacturers

recently issued.

And they talked about a pledge

to make the safety

and well-being

of vaccinated individuals

the top priority

in the development

of the first COVID-19 vaccine.

And they go on to talk

about industry sponsors will be

confident in the safety

and efficacy of any new vaccine

based on data

from rigorous, large clinical

trials,

including the expectation

that diverse populations are

included.



Now the pledge talks

about aspects that actually are

required as part of the drug

approval process.

So what was the impetus,

the reason for the manufacturers

to feel they needed to issue

this public statement?



RICHARD MOSCICKI: Well, John

I think you-- you said it.

This is something they do.

This is something they believe

in, and this is, uh,

standard operating procedure

to follow these rigorous testing

approaches in clinical trials,

um, as well as manufacturing

of--

of the products.

However, as you started out

saying, um, there is clearly

concern in the public,

uh,

within our current political

environment about whether there

will be undue pressure,

both on companies

or on the regulators

such as the FDA.



And we want to make

clear to the public

that in fact we are going

to follow

these rigorous approaches, uh,

to assure people that there will

be nothing different here.

This will be a vaccine that can

in fact pass all

the right safety and efficacy,

um, standards.



JOHN WHYTE: You know the pledge

talks about the desire

for a diverse patient

population.

But you and I know having worked

it together at the FDA,

that enrolling minorities

in clinical trials

can be challenging.

And I think we're seeing that

as part of COVID-19.

How confident are you that we'll

have enough of minority

populations

to know there is no-- what we

would call variability

of response

in different, you know,

subgroups?



RICHARD MOSCICKI: Well, that's

a great question, John.

You know, um, I think

for a long time industry, FDA,

and others have sought to make

sure that we increase the number

of various underserved

populations in clinical trials

so that we get that experience.

Um, but there are a lot

of reasons why historically it's

been difficult to do so.

There are trust issues

in the community.

There are financial concerns

for many

in those same communities.

Um, and there are access issues,

um, for many of them.



So today, um, the industry

is in fact embarked on a very

bold initiative

to try and address

these barriers as best as

possible

and in general increase,

um, the number

of these underserved populations

in clinical trials.

And particularly now

with COVID-19 vaccines

and treatments, uh, underway

and the impact that we've seen

on, uh, say,

the black community,

it's important, uh, that we try

to apply these um, these, uh,

approaches, uh, now.

And I think all the companies

are quite, uh,

interested in-- in using

such approaches that might

improve getting us,

um, a better sample.



JOHN WHYTE: And a lot of people

are tying the availability

of a vaccine to reopening,

whether it's reopening

of schools or businesses.

But I want to make you

aware of a recent poll

that we did it at WebMD

with results in other,

you know, media outlets where

they showed that almost 50%

of people

said they wouldn't get

the vaccine at all.

Less than 27% of people

said they would do it

in the first three months.



And the-- the issues are safety

in their minds, you know.

I'll let you take it first,

Dr. Moscicki, you know,

before I will.

Why do you think we're there?

Um, and how do we change

that mindset?

Because if we don't reach

a certain threshold

of vaccination in the community,

it's not going to have

the impact that we need.



RICHARD MOSCICKI: Well, I think,

unfortunately, there

is a segment of our population,

which, uh, has fallen victim to,

um, a, proposals that, uh, that

in fact vaccines

have caused, uh, a number

of issues

that I think scientifically

we know they do not.

Um, and that has provided

a background for some concern.

And some of that background

seems to be particularly

active in social media, ah,

today.



I think also, uh, we have been

moving with incredible speed,

ah,

in the industry

to try and address the pandemic

and to produce these.

And I'm sure that some people

are concerned that when you move

with such speed

it may cut corners, for example.



JOHN WHYTE: Well, I was going

to ask you about that.

Are we victims

of our own success?

You know, processes that took

years are now taking months.

And are we adequately explaining

that to the public?

Because it seems like, as you

said, we're cutting corners.

And it's just like in baking,

you can't, you know,

cut the temperature down or cut

the cooking time

or cut the ingredients.

I've tried and it's not

a good outcome.



Uh, but-- but are we explaining

that well enough?

I feel like in some ways

we're not getting that message

out.

And we use titles like warp

speed, which, you know,

when it comes to your body,

people might be saying,

you know, I don't want something

that sounds rushed.



RICHARD MOSCICKI: Yeah.

Well I think that's important

that we get that message out

that in fact we're not cutting

corners.

The difference in why we've been

able to do this so fast

has a lot

to do with the technology that's

been developed over time

by companies, the investments

they've made to be prepared to,

ah, use technology to move

in a fast way,

to work with the FDA

and other regulatory agencies,

ah, to work in a way that, um,

addresses in getting rid

of the sort of dead time,

if you will.



JOHN WHYTE: Yep.



RICHARD MOSCICKI:

So that the important time

that's being used

is used in a rigorous manner.

Um, we're not eliminating any

of the phases, ah, that are

important to testing a product,

either before they reach humans,

ah, or when they are in fact--



JOHN WHYTE: Right.



RICHARD MOSCICKI: --in people.



JOHN WHYTE: And in some ways

because there's so much virus

around, it actually provides

an opportunity to enroll

a sufficient number of people,

have them exposed to the virus

to test.

Isn't that correct?

So in some ways the fact

that it's so infectious

works to our advantage.



RICHARD MOSCICKI: Right.

You know, so-- so many

of the vaccines have already

passed what would be

an early stage of, um, testing

in people, the phase 2.

And we've seen, uh,

that these vaccines can produce

antibodies.

These antibodies look like they

should be protective.

But it is these very large phase

3's tens of thousands

of patients where we really get

to detect whether there could be

any kind of safety signals,

uh, where we really get to see,

uh, the impact that the virus

has to--

I mean, the impact

that the vaccine has--



JOHN WHYTE: Sure.



RICHARD MOSCICKI: --to really,

uh,

prevent the clinical problems

associated with the virus.



JOHN WHYTE: Well, let's talk

about, you know, the vaccine,

you know, trials, phase 3,

recent clinical hold.

A lot of people are saying,

you know what?

That shows that the system is

working, because they did what

they were supposed to do.

Put it all on hold, press pause,

and make sure that no one else

is at risk.

Can you comment on that, Dr.

Moscicki?



RICHARD MOSCICKI: No, I think

that's spot on, John.

You know, that is exactly what's

supposed to happen.

That's why you do these phase 3

trials.

And when you do see

a possible problem,

not-- you-- you have to find

out, is there a real problem?



JOHN WHYTE: Sure.



RICHARD MOSCICKI: Are there

more-- is there evidence

of anything more here?

Are there other people who might

have had a similar problem

and yet weren't detected now

that we've detected

this problem?

Um, and you want to do it

before you expose anybody else.

And that's why you put it

on hold, ah, until you really

have a thorough investigation

of what you saw.



JOHN WHYTE: Is 30,000 enough?

That's the number that people

tend, you know, talk about

in these phase 3 trials.

But, you know, in terms

of rare events,

let's say it's one in 10,000, 1

in 20,000, those might be

hard, you know,

to determine until you really

get it out there, as Dr. Offit

will talk about, to the first,

you know, few million doses.

Is that-- is that

a fair assessment?

As you know,

as we've talked

about in the past

that what we call these phase 4,

you know, trials where it's

on market, but we're still

surveilling in terms of safety

issues.



RICHARD MOSCICKI: Sure.

Well, look, uh, you know,

the phase 3 trials and the phase

2 trials, in addition,

will tell you about, ah, side

effects that, um, are so

common that you really begin

to worry about the risk

versus the benefit.



JOHN WHYTE: Sure.



RICHARD MOSCICKI: And that's

so important to know.

Um, the really rare events,

um, yes, it's often

necessary to track very

carefully what, um, has happened

to people who are vaccinated,

uh, after a product has been

approved, um, because it's

possible that there could be

these really rare events.

And to know about them

and to assess continuously

do they change the risk

versus the benefit

of the product.



JOHN WHYTE: You're

an immunologist by training.

I wanted to ask you if you could

take a couple of minutes

and explain the different way

these vaccines are working.

You know, some people

are believing that, you know,

they're being injected

with COVID-19.

Can you give a few minutes

and explain that

to the audience?



RICHARD MOSCICKI: Right.

So you're not being injected

with any kind of live virus

or a virus that in fact can now

cause disease.

That is not how any of these--

and there are probably

more than seven different ways

that these vaccines are

putting-- are put together.

But none of them bear any chance

of giving you COVID-19.

And technologies, like mRNA DNA

vaccines, these are not

combining

with your genetic material

at all

and, uh, pose

no meaningful genetic,

um, risk, uh,

from that standpoint.



Um, instead, what they're doing

and what the others are doing

is allowing, in the case

of the genetic material,

it allows your body to produce

a protein that could be related

to the virus that in--

or is related to the virus,

and um, that

is a tiny little fragment.

But it's an important fragment

that can get your body to see it

as foreign.

And then your body will make

antibodies, for example,

together with cells that

identify it as foreign

and can attack it.



And um, you know, in the more

standard approaches that are

genetic in basis, you're

actually using

that little tiny protein,

for example.

Um, and you may combine it

with something that in fact will

stimulate the immune response

against that little tiny

protein.

Um, and that, when you build up

enough of these antibodies

and some of these cells

that can react to it,

then your body when it's

confronted with a virus

has the ability to very quickly

attack and prevent that virus

from, uh, infecting.



JOHN WHYTE: Now

that's-- that's a good primer

for the audience in terms of how

these vaccines are working.

I want to ask you, Dr. Moscicki,

what are you hopeful for?



RICHARD MOSCICKI: Well, I'm--

I'm obviously hopeful that we

soon will have in fact

a safe and effective vaccine

and safe and effective

treatments, um, and whether one

comes first or the other,

we'll see.

We already have, um, treatments

that, um, do have an impact,

right?

I mean, there have been

over 1,400 clinical trials--



JOHN WHYTE: Wow.



RICHARD MOSCICKI: --about

substances

including 200

from the pharmaceutical

industry, ah, that in-- are

testing, uh,

a number of different agents.

And in these trials,

we've already seen Remdesivir

has an impact.

Uh, we already see

that old drugs like

dexamethasone uh, can really

be lifesaving, uh,

for many individuals.



And so I-- I'm--

I am confident that as we

continue this research

and as we continue to work, ah,

with the vaccines

and the many different vaccines,

I should even say, because it

gives us a lot of shots on goal.

Together with a number

of different therapeutic agents,

we are going to have

some effective ways to combat

this virus, um, and ah, bring

it, uh, together

because I think that science is

the way that we will get back

to normal.



JOHN WHYTE: And that's

a good approach.

The science is what's going

to get us out of this pandemic.

But Dr. Moscicki, I want

to thank you for taking time

today.

I want to thank you

for your leadership in terms

of the drug development process

as it relates to vaccine, as

well as other therapeutics

that you touched upon.

It's not just about the vaccine

right now.

And we look forward to talking

more to you

about how do we help consumers

understand

the safety of the vaccination

process,

that this is not

a process that's being rushed,

it's playing out as it should,

but in many ways

it's because of the innovations

that we've had

over the last few years.



RICHARD MOSCICKI: Absolutely,

John, those innovations,

those improved technologies

and the collaborations

are what are driving

the-- the really legitimate

speed and not the cutting

of corners.

Uh, it's really, again,

a very, um, strong, rigorous,

scientific process and testing

in clinical trials that are

being conducted today that I

think will get us these.



And we are all dedicated, not

just at this moment,

not just because there is

public concern,

but because that is

intrinsic to how we do business,

um, and how, um,

the scientific process works,

whether you're in a company

or whether you're

in an academic institution,

and-- or whether you're

a regulator.



I think it's very notable

that the FDA's, uh, center

directors, uh, their career, um,

scientists,

today also came out

with a statement, ah,

and very notable

that this statement, ah, is

again aimed to help

the public understand that they

see their duty, um, much

like the industry

does to continue to work

in a very rigorous way

to assure the safety

and efficacy of vaccines.



JOHN WHYTE: We're going to check

back in with you

as we continue to make progress

on this.

And thank you again.

And I want to thank our viewers

for watching Coronavirus

in Context.

I'm Dr. John Whyte.



John Whyte, MD, MPH. Chief Medical Officer, WebMD, Richard Moscicki, MD, Chief Medical Officer, PhRMA/delivery/aws/73/29/7329face-1fee-3a66-82f4-787f5739b455/Moscicki_091020c_,4500k,2500k,1000k,750k,400k,.mp409/11/2020 14:25:0018001200Moscicki_091020_1800x1200/webmd/consumer_assets/site_images/article_thumbnails/video/covid19-images/Moscicki_091020_1800x1200.jpg091e9c5e81fd6693

Traditional vaccines don’t usually work as well in the elderly, who are often the group most vulnerable to infections. Vaccine developers typically need to create special high-dose shots, or vaccines with added ingredients to stimulate the immune system -- called adjuvants -- in order to generate good protection.

“These findings could have profound significance if the protection afforded by vaccination among older adults is stronger than that of young adults because older adults are a very important target population for which we are targeting for protection with vaccination,” Chen says.

The purpose of the first phase was to assess safety and determine the most effective dose. Side effects seen in the first study included fatigue, chills, headache, muscle soreness, and pain at the site of the shot.

No placebo shots were given. Instead, recipients received two doses of either 25 micrograms or 100 micrograms given 4 weeks apart. The higher dose generated more antibodies in both groups. It also generated more side effects, including swelling and muscle soreness that lasted several days in some participants.

About 4 weeks after the 25-microgram shots, younger participants made an average antibody concentration of 323,945, while those ages 71 and up made an average concentration of 1,128,391 antibodies. After the 100-microgram shots, those ages 56-70 made an average concentration of 1,183,066 antibodies, compared to 3,638,522 in the older group.

The antibody responses measured in the study don’t necessarily mean that people are protected from infection. Researchers won’t know whether vaccination is protective until the end of the phase III trial, which is underway. But they are an encouraging sign.

“We were happy to see that the 100-microgram dose generated similar antibodies to those observed in 18- to 55-year-old recipients of the vaccine,” says Evan Anderson, MD, an associate professor of pediatric infectious disease at Emory University School of Medicine. The results from the younger adults were reported in an earlier study.

It’s not clear why this vaccine appears to generate such strong antibody responses, even among the elderly. “We don’t understand exactly why these immune responses in the older adults were still robust,” he says.

The study authors write that the antibody responses seen after the second dose of the vaccine are similar to those observed in patients who had recovered from COVID-19 and who had donated their blood for convalescent plasma. But they also note that right now, we don’t have a reliable biomarker that can tell us when someone is adequately protected against the virus.

The results were published today in TheNew England Journal of Medicine.

WebMD Health News Medically Reviewed by Hansa D. Bhargava, MD on September 29, 2020

Sources

The New England Journal of Medicine, Sept. 29, 2020.

Wilbur Chen, MD, professor, University of Maryland School of Medicine; chief, Adult Clinical Studies section, Center for Vaccine Development and Global Health, Baltimore.

Evan Anderson, MD, associate professor of pediatric infectious disease, Emory University School of Medicine, Atlanta.

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