[D66] Are We Looking for the Wrong Coronavirus Vaccines?

R.O. jugg at ziggo.nl
Mon Aug 24 17:16:01 CEST 2020


https://www.nytimes.com/2020/08/24/opinion/coronavirus-vaccine-prevention.html?

Are We Looking for the Wrong Coronavirus Vaccines?

The best vaccines don’t just prevent a disease; they also prevent the 
pathogen causing the disease from being transmitted. So why aren’t we 
focusing more on those?
By Adam Finn and Richard Malley
Dr. Finn and Dr. Malley are physicians specializing in infectious 
diseases and vaccinology.

Aug. 24, 2020, 5:01 a.m. ET

Not long after the new coronavirus first surfaced last December, an 
ambitious prediction was made: A vaccine would be available within 12 to 
18 months, and it would stop the pandemic.

Despite serious challenges — how to mass manufacture, supply and deliver 
a vaccine worldwide — the first prong of that wish could well be 
fulfilled. Eight vaccine candidates are undergoing large-scale efficacy 
tests, so-called Phase 3 trials, and results are expected by the end of 
this year or early 2021.

But even if one, or more, of those efforts succeeds, a vaccine might not 
end the pandemic. This is partly because we seem to be focused at the 
moment on developing the kind of vaccine that may well prevent Covid-19, 
the disease, but that wouldn’t do enough to stop the transmission of 
SARS-CoV-2, the virus that causes Covid-19.

Doctors usually explain vaccines to patients and the parents of young 
children by describing how those protect us from a particular disease: 
An attenuated form of a pathogen, or just a bit of it, is inoculated 
into the human body in order to trigger its immune response; having 
learned to fight off that pathogen once, the body will remember how to 
fend off the disease should it be exposed to the same pathogen later.

A vaccine’s ability to forestall a disease is also how vaccine 
developers typically design — and how regulators typically evaluate — 
Phase 3 clinical trials for vaccine candidates.

Yet the best vaccines also serve another, critical, function: They block 
a pathogen’s transmission from one person to another. And this result, 
often called an “indirect” effect of vaccination, is no less important 
than the direct effect of preventing the disease caused by that 
pathogen. In fact, during a pandemic, it probably is even more important.

That’s what we should be focusing on right now. And yet we are not.

Stopping a virus’s transmission reduces the entire population’s overall 
exposure to the virus. It protects people who may be too frail to 
respond to a vaccine, who do not have access to the vaccine, who refuse 
to be immunized and whose immune response might wane over time.

The benefits of this approach have been demonstrated with other 
pathogens and other diseases.

The Haemophilus influenzae type B (Hib) conjugate vaccines were 
designed, and licensed in the early 1990s, to prevent young children 
from developing serious infections such as meningitis. Soon enough an 
unexpected and welcome side benefit became clear: The vaccine 
interrupted the bacterium’s transmission; after its introduction, 
occurrences of the disease dropped also in groups that had not been 
vaccinated.

The human papillomavirus (HPV) vaccines were developed to prevent 
cervical cancer and genital warts in women. They have proved immensely 
effective among the women to whom they are administered — and up to 50 
percent effective at preventing genital warts among unvaccinated men, 
according to a 2017 study of the health insurance records for 2005-10 of 
some nine million people in Germany.

To understand why this is the case, remember what it takes for you to 
become ill from a pathogen, be it a virus or a bacterium.

First, you are exposed to it. Then it infects you. While you are 
infected, you may infect others. In some cases, the infection develops 
into a disease. In other cases, it doesn’t: Though infected, you remain 
asymptomatic.

One way that vaccines can interrupt a pathogen’s transmission cycle is 
by preventing the pathogen from causing an infection in the first place. 
This is how many common vaccines — against measles, mumps, rubella and 
chickenpox — operate.

Other vaccines — like the ones against meningococcal meningitis or 
pneumonia brought on by the pneumococcus bacterium — can block the 
transmission of the pathogen by interfering with the infection or by 
decreasing either the quantity of pathogen that the infected patient 
sheds or the duration of the shedding period.

Some recipients of the pneumococcal pneumonia vaccine simply don’t get 
infected with the bacterium; others do get infected and carry the 
bacterium in their nose, but in smaller amounts and for shorter periods 
of time than if they had not been vaccinated.

Much still needs to be learned about precisely how such mechanisms work 
— what part do antibodies play? T cells? — but the upshot from these 
examples is this: Vaccines can block the transmission of viruses or 
bacteria, and they can do so in several ways.

Given the communitywide benefits of accomplishing that, especially in a 
pandemic, current vaccine-development efforts should prioritize finding 
vaccines that limit the transmission of SARS-CoV-2.

The U.S. Food and Drug Administration has stated that preventing a 
SARS-CoV-2 infection is in itself a sufficient endpoint for the Phase 3 
trials of vaccine candidates — that it is an acceptable alternative goal 
to preventing the development of Covid-19. The World Health Organization 
has said that “shedding/transmission” is as well.

These guidelines are an important signal, especially considering that 
the F.D.A. has never approved a vaccine based on its effects on 
infection alone; instead, the agency has focused exclusively on the 
vaccine’s effectiveness at disease prevention.

And yet vaccine developers do not seem to be heeding this new call.

Based on our review of the Phase 3 tests listed at ClinicalTrials.gov, a 
database of trials conducted around the world, the primary goal in each 
of these studies is to reduce the occurrence of Covid-19.

Four of the six Covid-19 vaccine trials for which information is 
available say they will also evaluate the incidence of SARS-CoV-2 
infections among subjects — but only as an ancillary outcome.

This approach is shortsighted: One cannot assume that a vaccine that 
prevents the development of Covid-19 in a patient will necessarily also 
limit the risk that the patient will transmit SARS-CoV-2 to other people.

For example, a study of young Australian teenagers published in the New 
England Journal of Medicine early this year found that the vaccine used 
to prevent the diseases caused by the B strain of meningococcus in 
children and teenagers “had no discernible effect” on the presence of 
the relevant bacterium in the throats of vaccinated subjects displaying 
no symptoms.

The inactivated polio vaccine prevalent in many developed countries 
today, known as IPV, is highly effective at protecting individuals 
against polio. But it is far less effective at reducing viral shedding, 
at least in fecal excretions, than the oral vaccine, known as OPV, used 
more widely in other parts of the world.

In the late 1990s, the United States, like other wealthy countries, 
replaced with an acellular vaccine the killed-whole-cell pertussis 
vaccine it had previously used against whooping cough. A resurgence of 
whooping cough already was underway, but it accelerated then: Although 
the new vaccine was better than the previous one at protecting the 
inoculated from the disease, it was less good at blocking transmission 
of the bacterium that causes the cough.

Conversely, a vaccine that, let’s say, offers older adults only modest 
protection against developing a disease might nonetheless be very 
effective, when administered to healthy adults or children, at curbing a 
pathogen’s transmission in a population overall.

This is the case with the pneumococcal conjugate vaccine. A 2015 study 
published in the New England Journal of Medicine found that the vaccine 
reduced the occurrence of pneumonia in inoculated adults age 65 or older 
by only about 45 percent. Yet, according to a study last year by 
researchers at the Centers for Disease Control and Prevention and 
Stanford University, the immunization of infants and toddlers reduced 
ninefold the incidence of pneumococcal disease in the elderly.

With some vaccines, for some diseases, the indirect benefits of 
vaccination can be greater than the direct effects.

Based on these precedents, it could be a grave mistake for vaccine 
developers now to hew only, or too closely, to the single-minded goal of 
preventing Covid-19, the disease.

Doing so could mean privileging vaccines that don’t block the 
transmission of SARS-CoV-2 at all, or abandoning vaccines that block 
transmission well enough but that, by prevailing standards, are deemed 
to not forestall enough the development of Covid-19.

That, in turn, would essentially mean that the only way to ever get rid 
of SARS-CoV-2 would be near-universal immunization — a herculean task.

Focusing on how to block the coronavirus’s transmission is a much more 
efficient approach.

This is why randomized controlled trials of the vaccines currently under 
consideration should include regular monitoring for the presence of 
SARS-CoV-2 in study subjects. The goal should be to evaluate whether the 
subjects acquire the infection at all, and for how long, as well as how 
abundantly they shed and spread the virus, when and how.

Studying these issues could also help cast a light on the role of 
so-called superspreading events in this pandemic.

More and more research suggests that a very small number of instances — 
gatherings at restaurants or bars, choir rehearsal, funerals, church 
services — might account for a vast majority of the cases of infection 
overall.

But the discussion about those instances has tended to focus on their 
settings and circumstances, such as the presence of crowds in confined 
spaces for extended periods of time.

Yet the question of whether some infected individuals, perhaps 
especially at certain stages of infection, are particularly infectious — 
whether they, themselves, are superspreaders — also needs to be studied 
head-on: When does contagiousness peak in whom and why? And can vaccines 
modify any of that?

The best vaccines don’t just protect the inoculated from getting sick 
from a disease. They also protect everyone else from even contracting 
the pathogen that causes that disease.

Preventing the very transmission of SARS-CoV-2, no less than stopping it 
from turning into Covid-19, should be a main priority of current efforts 
to develop the vaccines to end this pandemic.

Adam Finn (@adamhfinn) is a senior clinician in the pediatric immunology 
and infectious diseases clinical service at Bristol Royal Hospital for 
Children and a professor of pediatrics at the University of Bristol. 
Richard Malley (@rickmalley) is a physician specializing in infectious 
diseases at Boston Children’s Hospital and a professor of pediatrics at 
Harvard Medical School.



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