C O V ID-19
‘India needs to spread its bets on vaccines’
Interview with Dr Satyajit Rath, Indian Institute of Science Education
and Research, Pune. BY V . S R I D H A R
IN THE WAKE OF THE PANDEMIC, COUNTRIES
and companies have raced to develop and deliver
COVID-19 vaccines at an unprecedented pace. Vaccines
have been developed across several technology plat-
forms, each of which has disadvantages as well as advant-
ages. As the pace of India’s vaccine drive stalls
dangerously, and even as the possibility of “vaccine es-
cape” variants cloud the prospects for the future, there is
an urgent need for countries to stay at the cutting edge of
vaccine design to counter the pandemic.
Navigating through the apparent clutter of vaccine
technologies, their design methodologies, and their po-
tential drawbacks, Dr Satyajit Rath,
eminent immunologist, physician and
pathologist, spoke to Frontline. Rath is
now associated with the Indian Insti-
tute of Science Education and Re-
search (IISER), Pune. Excerpts:
There are several ways to make
vaccines. What determines the choice
of technology platform? How do they
reflect the disease perspectives that a
specific vaccine seeks to address?
In the first place, all vaccines are
biological products. There is a funda-
mental difference between traditional
drug manufacturing and small mo-
lecule drug manufacturing and vaccine
manufacturing. That is why many of the biological phar-
maceutical manufacturers, rather than small molecule
drug producers, find it easier to manufacture vaccines.
The second point is that at the manufacturing level
what the disease is is really immaterial to the manufac-
turer. That is true of small molecule drug manufacturing
too. It is the integrity of the chemical synthesis and
purification processes that are important. What the drug
will eventually be used for is immaterial as far as the
manufacturer is concerned.
I understand… that there is an element of being
agnostic…
Yes, to the ultimate usage. There is a whole generic
suite of manufacturing technologies involving biologics
FRONTLINE . JUNE 18, 2021
that are brought into play. But the specific nature would
depend not on the disease they seek to address but on the
vaccine design platform they [the manufacturers] seek
to use.
What drives the choice of a particular platform?
Ah! This is where we come to a set of specific de-
cisions in which the biomedical science and the manufac-
turing design and processes intersect with each other. Let
me explain this. Vaccine design platforms fall into two
broad categories. Essentially, all vaccines in some form
are mimics of the original infectious agent. They are
basically designed to fool the body’s
immune system into making a re-
sponse. We know that the vaccine is
not going to cause any serious damage,
but you are still providing enough cues
to the immune system for it to think
that it is worth responding to. Essen-
tially, you aim to deliver to the im-
mune system target molecules that
resemble the original infectious agent.
Whether it is one target or many is
immaterial.
The vaccine design falls into two
categories. In one design you make the
target in the manufacturing process
and introduce it into the body. In the
other, during the manufacturing pro-
cess you make the genetic code that specifies the target,
then you introduce the genetic code into the body and let
the body make the target and respond to it.
Can you please explain this process?
Hopefully, if I explain using the specific platforms
that fall into the categories as examples, it may be easier
to understand. The first is manufacturing the target out-
side and then introducing it. Let me give you two differ-
ent COVID-19 vaccines in two different forms. One is
Covaxin, in which you are making the target, in this case
the whole virus, in the manufacturing process and then
introducing it into the body. The other vaccine in the
same category is the Novavax vaccine design. In this case,
the idea is not to make the whole virus but just the spike
30
protein as a recombinant protein and introduce it in an
appropriate formulation into the body. In both these
cases, although the manufacturing processes are radic-
ally different, what you are doing is manufacturing the
target, formulating it and then injecting it.
Completely different from this targeting process are
the RNA and DNA-based COVID-19 vaccines. The first
are the ones by Moderna and Pfizer-BioNTech—the
mRNA vaccines. They make the RNA chain that codes
for the spike protein. The mRNA is then packaged so that
when it is injected and gets to the cells, the cells will
simply translate it into proteins. Basically, this process is
about manufacturing the genetic code, not the final
product: introducing the genetic code into the body and
letting the body make the target and respond.
This is also the case with the Zydus Cadila vaccine
under trial. In this case, the attempt is to use DNA
instead of RNA, but the principle remains the same. The
DNA molecules are first introduced into the cell. It is
then read by the RNA molecules, which convert it into a
specific protein.
The third platform in this category is the widespread
adenovirus vectored vaccines. (Adenoviruses are double-
stranded DNA viruses which cause mild respiratory and
gastrointestinal tract infections. They are considered ex-
cellent vehicles for delivering target antigens in mam-
mals). Essentially, you are introducing the SARS-CoV-2
spike protein genetic sequence into the adenoviral ge-
netic sequence. Then you are using the adenovirus as a
delivery vehicle to get into cells. Once it gets into the cells,
the same process repeats itself, as with other platforms.
In all these three cases, what is introduced into the
body—-that is, what is being manufactured—is not the
target but the genetic code of the target. The vaccine
consists of the genetic code introduced into the body.
However, if you take the protein subunit or viral
particle or the whole inactivated virus, or even, eventu-
ally, infectious viruses—all of these methodologies use a
target that is made in the manufacturing process and
then introduced into the body. The reason I am making
this categorisation arises from the fact that the manufac-
turing constraints are quite different in the two categor-
ies.
What in the nature of the biologics makes the
manufacturing platforms different or difficult?
They are different for an interesting biological
reason. When you make the code, it does not have a
31
shape, it only has a sequence. The exact shape of the RNA
or the DNA really does not matter because it is going to be
read as a sequence, one after another. Therefore, all you
have to ensure is that the sequence manufactured is right.
On the other hand, to make the target in a manufac-
turing process and then introduce it into cells, we need to
make sure that the target, a protein, is folded into a
three-dimensional structure which resembles the ori-
ginal virus as closely as possible. Otherwise, you are going
to create an immune response that does not recognise the
virus. This has been Novavax’s problem. Recall that it has
twice delayed its clinical trials.
One of the reasons is that it has had protein-folding
problems. That problem is shared with all other biologics
manufacturers such as those manufacturing monoclonal
antibodies. All of them use protein manufacturing tech-
nologies. All of them share the problem of having to make
certain that the final folded shape of the protein is accur-
ate and consistent.
MANUFACTURING PROCESS
Getting that right is problematic. Is that what you are
saying?
Exactly. You now begin to see why the RNA vaccines
came up much earlier than the protein vaccines. The only
way you can be reasonably certain—in a manufacturing
sense—that the folded shape is good is by actually grow-
ing the virus! If you take a cell line and grow the virus—
SARS-CoV-2 is itself a cell line—in a manufacturing
process, then you know it is correctly folded because it is
made as part of the virus construction. This is the reason
why the inactivated virus vaccines were designed as such
and this is why they, along with the mRNA vaccines,
arrived earlier. Note that the Sinopharm and Covaxin
inactivated viral vaccines thus arrived earlier than the
others.
Where does the Oxford AstraZeneca vaccine stand in
this categorisation?
This vaccine is an adenovirus vaccine. It falls in ex-
actly the same category as the RNA, DNA and the aden-
oviral vector vaccines. Instead of chemically packing the
RNA—which is what the mRNA vaccines are—here it is
biologically packaged into the carrier adenoviral vector.
But here, you don’t have to worry about whether the
SARS-CoV-2 target that you have introduced is correctly
folded or not. In a manufacturing sense, the RNA, DNA
FRONTLINE . JUNE 18, 2021
and adenoviral vector vaccines are much more robust
than the protein subunit manufacturing process.
Why would someone choose such a challenging option
at such a time?
That depends on whether you are asking why protein
folding is a problem.
No, I am asking why would someone choose such an
obviously more difficult path…
That is a great question because the likes of Pfizer and
AstraZeneca keep hoping that nobody will ask this. If you
look at the amount of spike-directed antibodies gener-
ated by the Novavax vaccine candidate in people, those
amounts are larger than the amounts generated by the
mRNA and adenoviral vaccines.
How much more in terms of quantities?
(Laughing). I am laughing because I knew you would
ask me this. The point that I keep making is that we have
adopted a neoliberal solution to a public health problem.
Thus, none of them [vaccine manufacturers] is willing to
conduct comparative trials with each other. As a result,
we do not have any comparative figures at all. I am basing
this simply on the preclinical data—what happens when
you immunise mice—with mRNA versus DNA versus
whole protein vaccines. In mice there can be 4-5-fold
higher levels in antibody levels. This is perhaps why a
company like Novavax, whose forte is protein-based
design, knows that if it can solve the protein folding
problem, it will have a vaccine that can generate antibody
levels that are far higher than the others.
Also, keep in mind what the ICMR [Indian Council of
Medical Research] is saying about the so-called Indian
variant, that 50 per cent of the vaccine-generated anti-
bodies bind to the “Indian variant”. This is a complex
matrix, based on how much of the antibodies bind to the
variant and how much are the total antibodies generated.
If the total is very high, then even if a faction binds to the
variant, it will be enough to provide protection. So, there
is a lot of utilitarian complexity.
SCALING UP CAPACITY
We are in a situation of an acute shortage of vaccines.
What do you think is really the problem for companies
in scaling up capacity after having achieved
breakthroughs in developing the vaccines?
Let me start by being rude. I do not think there has
been any breakthrough in any of this. Keep in mind that
the mRNA and the adenoviral vaccines, the major vac-
cines being used the world over, are tweaked versions of
vaccines that these exact same groups had developed, not
today, but 10-15 years ago, against SARS-CoV-1 and
MERS-Cov (Middle East Respiratory Syndrome). All of
them had been to some extent road-tested. So, it is not as
if we have miraculously made vaccines within months. It
is just that we had been doing this sort of stuff for a long
time but we had decided to let the market decide whether
FRONTLINE . JUNE 18, 2021
to complete the trials. And, because those viruses were no
good at person-to-person transmission, simple physical
separation, care and isolation terminated those little out-
breaks. Thus, advanced vaccine prototypes were sitting
on the shelf. All that Sarah Gilbert’s group at Oxford did
was to take it from the shelf, dust it off and tweak the
sequence from the SARS-CoV-1 spike protein to the
SARS-CoV-2 spike protein. And, hey presto, you have the
vaccine. It is important for all of us to recognise that this
was not a major breakthrough. This is the outcome of
cumulative science. This is the outcome of sustained
global investment in open-ended efforts.
But that said, the scale of constraints would be differ-
ent for each of these platforms. But this is where we get
into separating the matrices. So, let me try a two-dimen-
sional matrix or a kind of SWOT analysis, where we are
talking about advantages and limitations.
Think of the Covaxin technology platform. You grow
the virus in tissue culture and inactivate the virus. Essen-
tially this is what Louis Pasteur’s students used to do in
animals while developing the rabies virus—a century-old
technology. It was actually grown in animals. Even dur-
ing our childhoods, the rabies vaccine was developed in
infant mice. But the principle remains the same: you
grow the virus, you purify it and then inactivate it and
then package it for injection. Growing the virus in anim-
als is easy because it is low-tech maintenance for an
assembly line. But the difficulty is that you get a lot of
animal product contamination in the virus preparation;
this was the problem in our childhood when we used to
have 21-shot vaccines for dog bites. The answer to that
was to clean up the virus growing technology. The second
step in cleaning up the virus growing technology is what
is done even today. Every year the world makes com-
pletely new influenza vaccines. And, those are made in
the extraordinarily ancient, stable, low-tech method of
manufacture which is this: grow the virus, inactivate it
and package the virus for injection. But in the case of
influenza vaccines, you don’t grow it in animals; instead,
you grow it in chicken eggs, which is cleaner and easier to
maintain than in growing the virus in live animals. That
is the technology.
What are the constraints to scaling up?
You can see that the growing of the virus is fairly low
tech as long as you are growing it in eggs. But as soon as
you bring it to cell culture in bioreactors, you up the ante
as far as the technology is concerned because growing
cells in bioreactors is a much more finicky process. They
have to be grown in sterile conditions, your nourishing
fluid has to be available, it has to be just so, it must have
just that many ingredients, all of which must be readily
available. As a result, supply chain problems multiply
because you need ancillary industries that ensure reliable
supplies of materials and equipment. Sterility becomes a
problem in the bioreactors because the contents are nu-
trient-rich. If sterility is breached, all sorts of fungal and
bacterial stuff begin to grow, and upset the whole thing.
As a result of all this the whole thing becomes essen-
32
“Why did the government not
give the vaccine [Covaxin] to a
dozen different biologics
manufacturers?”
tially a biologics manufacturing technology. Remember
that monoclonal antibodies are made in cell lines exactly
like these. Any company that makes biologics can make
vaccines.
But here is your problem: what you are growing is an
infectious virus. If I grow infectious viruses in very small
amounts it is not a problem. But if I grow a larger amount
in the same place, an even larger amount, and a still
larger amount, the potential catastrophic biosafety prob-
lem begins to amplify. Between growing the virus, har-
vesting, cleaning it up and inactivating it, you are left
handling live infectious and dangerous viruses. And, the
problem is that biosafety containment needs to be prop-
erly and robustly backed up. I don’t mean to create panic
with an analogy that I may be careful to use in public, but
you are creating exactly the same kind of a situation that a
nuclear reactor poses. It is a low-likelihood event, but the
consequences can be catastrophic. This is the crucial
difference between growing infectious SARS-CoV-2
virus in the manufacture of inactivated vaccines and
growing adenovirus in the adenoviral vector vaccines
because the latter virus is not dangerous. So, it does not
need the containment that the vaccine manufacturing
process from actual infectious virus requires. This is a
great limitation of the infectious virus technology in
scaling up.
How have the other manufactures of infectious virus-
based vaccines, such as Sinopharm, coped with this
problem?
They have not put all their bioreactors in one loca-
tion. They have spread them out. Basically, you spread
them out and limit the amounts handled in a single
location in order to reduce risk. Geographically spread-
ing out the production makes it possible to reduce risk in
a single location.
This is the reason why many of us, including people
like me, have been for long puzzled. Here is the problem:
the Indian Council of Medical Research made this vac-
cine and gave it to BBIL. Why did the government not
give the vaccine to a dozen different biologics manufac-
turers? All it needed to have done was to ensure geo-
graphical decentralisation, while ensuring large-scale
production. What was the problem in doing this? It is
only now that they are talking about this.
But what about the other vaccine platforms, what are
their problems in scaling up?
As far as the mRNA vaccines are concerned there is
33
really no biological processes involved. There are no live
cell processes involved. It is much more of a chemical
technology. As a chemical technology, it in some ways
makes manufacturing easier. You do not have to worry
much about nutrient fluids, sterility so much—you al-
ways do, but not so much. But on the other hand, the
number of building units you need is enormous. You are
building mRNA from scratch, you are building massive
molecules from scratch, using enzymatic as well as non-
enzymatic processes, none of which is easy and straight-
forward. You can use biologic pathways but then you
come to biologics technologies, and those are not easy. In
all this a fair amount of detailed know-how in terms of
tricks of the trade—I am very reluctant to use the term
intellectual property—is involved. But tricks of the trade
can be understood and assimilated if there is a level of
upskilling already available in the manufacturing tech-
nologists human resource pool. All of these become po-
tential roadblocks.
In fact, quite apart from what Bill Gates has said
about vaccine manufacture and intellectual property
rights and manufacturing in the Global South, I see it to
some extent as the white man’s burden kind of perspect-
ive. But, apart from that politics, he has a point: it is not
simply patents, it is these tricks of the trade, ability to
assimilate and operationalise the tricks of the trade. This
depends on whether you have sufficiently upskilled hu-
man resources in the manufacturing sector.
You have to learn to do it…
You have to be able to learn to do it. You must have a
sufficiently sophisticated background and capacity
already in order to be able to learn to do it. This is a
limitation in building the mRNA platform.
Moreover, there is a short time-window problem. As
mRNA manufacturing base expands, it is in the nature of
things that the manufacturing technologies will spread to
the Global South in a relatively short time. But there is
also the issue of QA-QC (Quality Assurance and Quality
Control) that for mRNA sequencing have to be extremely
finicky because you want the exact arrangement. And,
because you are building that sequence batch by batch,
unless you use biological processes you need a lot of
step-side quality control. This is because you are building
a long chain of the RNA brick by brick. So you need to run
the QA-QC protocol every few bricks at a time. That
makes for a slow and cumbersome component of the
manufacturing process. These are the issues with the
mRA technologies.
Let me go further. When the RNA is introduced into
your body, there are so many enzymes that damage the
RNA. Remember, the RNA is a very delicate molecule.
This requires that the RNA is packaged. Packaging re-
quires two properties: one, it must protect the RNA, and
two, it must help to deliver the RNA inside cells. This is
why the nano lipid formulation that Pfizer and others
talk about—that their vaccine is a nano lipid formula-
tion—is essentially encasing the RNA in a fat droplet.
This is to ensure that water and water-based damaging
FRONTLINE . JUNE 18, 2021
agents do not get to the RNA. And, since all our cell
linings are made up of fat, this fat and that fat can sort of
stick together and allow the RNA to get absorbed. The fat
packaging is highly specific and with high degree of
purity in terms of components used. This again causes
you to run into supply chain problems. You need not only
a highly specialised, but a diverse supply chain to run the
manufacturing process.
GEOGRAPHICAL FOCUS
Are mRNA platforms easier to manage because the
supply chains are more closely integrated spatially as
well as qualitatively?
I would think that the mRNA platform would depend
much more on a diverse supply of fine chemicals than
biologics technologies. It is in the nature of the develop-
ment of these technologies that, inevitably, there has
been a geographical focus in the availability of these
intermediate fine chemicals. But I suspect that this, like
the tricks of the trade advantage I mentioned earlier, is
temporary. What does it take to set up a fine chemicals
ancillary industry? The Global South does not set it up
because it does not see a credible market for it. If there is a
credible local market for using mRNA technologies that
source materials from them, they will set it up. The
advantages that the entities in the West enjoy now is
likely to be transient, a few years at the most.
Based on the description I have given of the manufac-
turing platforms—between using infectious viruses at
one end and making the RNA at the other end—you will
appreciate that the major technologies that are being
used and spreading rapidly are those based on adenoviral
vaccines. This is because the adenoviral platform does
not involve a chemical manufacturing process. Once the
innovator has designed and built the adenovirus and the
cell line for it to grow in, all that a generic biologicals
manufacturer has to be given are the cell line and the
adenovirus. So, someone like the Serum Institute of India
[SII] can keep upscaling its capacity, unless interrupted
by fire. There is no real difficulty, pretty much anybody
can do it. There are manufacturers in South Africa, Ar-
gentina, Malaysia, Thailand, Korea and many other
countries who can do this. This has become a widespread
technology platform because it is built on the basic man-
ufacturing skeleton of widespread biological drug manu-
facturing of cell line and of products in bioreactors.
So, is it just the exclusive licence given by AstraZeneca
to SII that has been a hindrance to the wider dispersal of
vaccine capacities in the Global South?
Aha! It is not a matter of exclusive licence given to SII.
It is a matter because SII is a subcontractor of As-
traZeneca. Basically, AstraZeneca is holding the IP and
has contracted SII to manufacture it in India. Every dose
that goes out of SII’s doors has the approval from As-
traZeneca.
Let me rephrase. If not for this legal stipulation, would
FRONTLINE . JUNE 18, 2021
there not have been many more Indian companies
manufacturing the vaccines?
It is a mystery why ICMR, which is controlling the IP
on Covaxin, chose to give it exclusively to BBIL. From a
public health perspective, that would have been the sens-
ible thing to do. The so-called AstraZeneca vaccine,
which I never refer to as the AstraZeneca vaccine—I
always call it the Oxford-AstraZeneca vaccine just as I
always refer to the so-called Moderna vaccine as the
NIH-Moderna vaccine—was developed at Oxford. Sarah
Gilbert’s team has been working on adenovirus vector
vaccines for 25 years, funded entirely by U.K. taxpayers.
In fact, Sarah Gilbert and Andrew Pollard made the
announcement last March that they were developing the
vaccine. They also said it would be available in the public
sector.
Why was the property of the people of the United
Kingdom sold to AstraZeneca? Once the British govern-
ment sold it to AstraZeneca, why would AstraZeneca
contract more manufacturers to produce the vaccine
than it needs? After all, for the for-profit sector it is
always preferable to have a desired product in short
supply. That is the logic of the marketplace. Why hasn’t
AstraZeneca contracted another 35 different companies
which have proven capacities the world over by simply
giving them the protocol, the cell line and the adenov-
irus? That is all they need to make the vaccine. The short
answer to that is if this had happened AstraZeneca would
not be as important, where people go begging to them.
The public sector, the people and governments threaten-
ing companies is paradoxically a measure of the pivotal
importance these companies have acquired. That will
translate into non-financial clout.
So, we have two models—one implemented by
AstraZeneca with Covishield and the other by the Indian
government with Covaxin—which are mirror images of
each other.
Pretty much. Can BBIL manufacture the As-
traZeneca product? Of course, it can. If it can make a cell
line and grow a virus from it, it can grow another cell line
and grow another virus. In fact, BBIL has a separate deal
with the Washington University School of Medicine in
St. Louis to make an adenoviral nasal vaccine. It is
already growing an adenoviral cell line. This is just em-
pirical evidence to support my contention.
What may be BBIL’s constraints?
I suspect the increasing requirements for biosafety of
an infectious virus places an additional constraint on
upscaling. This is why, I think, BBIL has very reluctantly
allowed ICMR to license other companies to produce
Covaxin. But that is going to take time. There is a learning
curve involved in all this. For pity’s sake, Haffkine Bio-
Pharmaceutical Corporation Ltd is, I am sorry to say, an
utterly moribund company, like many other vaccine
PSUs. And, this has happened because of the way govern-
ments have treated them over the last 30 years.
Regarding Covishield, I suspect what Adar Poon-
34
awala has been saying, about not having the money, may
probably be correct. Why did the U.K. government, the
WHO, the Government of India, the United Nations, not
intervene and tell AstraZeneca: hey, Zydus Cadila can
manufacture, so can Cipla, Torrent, Dr. Reddy’s, Biolo-
gical E, Shanta Biotech, all these companies can manu-
facture, so why don’t you distribute the licences?
Similarly, South African, Korean, Argentinian compan-
ies and others around the world could have been asked to
produce. Why was this not done? The short answer to
that question is that this is what happens when you apply
a neoliberal solution to a public health problem.
The scale of human suffering puts more and more
pressure on the companies. But the companies are not
pressed by politics alone, they are pressed by actual
suffering. Until the suffering is visible, pressure does not
grow on the companies. And, that is what we are seeing.
Even if they want to scale up, the supply chains will
take at least 2-3 months to set up. The bioreactors have to
be imported. All this will take time. Setting up and
upscaling the infrastructure in PSU units will take time,
money and human resources. Equipment, setting up
protocols, testing, etc., will take time and money.
The mRNA technologies appear to be succeeding and
they have an interesting future manufacturing trajectory.
They are going to be useful for not just vaccines but for
other drug-like products. Now that there is proof-of-
principle out there, the mRNA technologies are going to
be part of the ecosystem. I think over the next three to five
years, we are going to see supply chain components
emerging in the Global South. We will begin to see fine
chemical components that go into mRNA platforms de-
velop as ancillaries to the supply chain in these countries.
NEGLECT OF PUBLIC SECTOR IN BIOLOGICALS
Given the overhang of neglect of the public sector in
biologicals in general and vaccine manufacturing in
particular, what would it take to revive them? And, how
long would it take?
That can be done in a year. Because we have public
sector vaccine manufacturing entities that already exist,
even if in a moribund state, it would take only political
will and financial muscle to revive them. Enthusiastic
recruitment of skilled professionals, re-equipping and
revitalising them and expanding them should be possible
within a year.
If you had a 3-5 year perspective plan for these units, as
well as involving private companies operating in this
field, how much would you need to spend for building
such an ecosystem?
I honestly have no idea about this. But if SII was paid
about Rs.3,000 crore for ramping up its capacity, it may
perhaps cost about twice as much to expand capacities in
public sector units.
Expansion of capacities would also give leverage to the
government indexing with SII…
35
Exactly. Not just with SII, it will give leverage with
AstraZeneca or with any other vaccine company.
Would some platforms be better suited to address the
pressures from new vaccine escape variants?
In a sense, the way we are measuring vaccine effect-
iveness is like the man who lost his ring in the darkness
but is searching for it under the light because that is
where the light is. What we are trying to detect is what we
already know how to detect, which are the so-called
neutralising antibodies. This is how we are detecting and
correlating the effectiveness of all the vaccines. But neut-
ralising antibodies actually interrupt the transmission
cycle. So, it is logical that if the virus changes to improve
its transmissibility, it is almost as a byproduct that it will
have some effect on the neutralising antibody mechan-
ism.
Does India need to spread its bets on vaccines?
Absolutely. No question about that. We badly need to
spread our bets—platform-wise as well as capability-
wise. Let me give you an example. I do think that the
adenoviral vector vaccines have a problem. If we generate
very high levels of antibody responses to the adenovir-
uses, it is possible that later the vaccines based on the
same design might run into difficulties, particularly in
populations that have been recently immunised with
vaccines of the same platform.
This is because we are injecting a whole adenovirus.
The body is generating response to not just the target but
also the adenovirus. As a result, when the next time an
adenovirus injection is given, adenoviral antibodies may
prevent the target from getting into cells. We ought to be
mindful of this problem and also invest in mRNA
vaccines.
Let me point out that the Novavax approach, which is
based on the protein subunit approach, is a much more
focussed approach. It is a much more traditional biolo-
gics approach in the sense that you make a functional
protein, mix it with an adjuvant and then inject it. It
generates very targeted antibodies and does not generate
these toxic cells. It is a very narrow platform, but it is not
something we should ignore.
This is partly exemplified by what my friend
Raghavan Varadarajan (biophysicist at IISc, Bangalore)
is doing. What Mynvax is doing (and published in a
journal recently) is making a Novavax kind of spike
protein on a very biologics-friendly technology platform,
but generating extremely high level of antibodies and is
temperature stable. So, the vaccine formulation may not
even need refrigeration. So, there are different advant-
ages to different formulations. I am giving you this ex-
ample in order to underline the fact that we need to hedge
our bets by building as large and diverse a portfolio as
possible. !
Full disclosure: Satyajit Rath is an adviser to Mynvax, a
company incubated at the Indian Institute of Science,
Bengaluru. Mynvax was founded by Raghavan Varada-
rajan in 2017. It is developing a COVID-19 vaccine.
FRONTLINE . JUNE 18, 2021