The
early wave of Covid-19 vaccines appear unlikely to deliver a
complete shield against getting the infection, as (say) a
measles inoculation comes close to providing. They seem more
likely to resemble a flu vaccine. Meaning: they will reduce
(but not eliminate) the risk of contracting the disease, and
will also hopefully reduce the risk of experiencing severe
symptoms should an infection occur. We are going to need to
be realistic about what even a relatively successful vaccine
can deliver. Set the expectations too high and the outcomes
could easily erode public trust in the entire vaccination
programme.

To repeat : if and when the first crop of
Covid-19 vaccines arrive , their prime role will be to help
control the spread and severity of the disease, rather than
preventing infection entirely. The first entrants on the
market are unlikely to be the best an final option. Ideally,
as Dr Greg Poland head of Vaccine Research at New York’s
famed Mayo Clinic has indicated, it would be great if a
Covid-19 vaccine could produce lasting immunity from a
single dose, but that’s a long way off. Poland
believes the
following timeframe
(lightly edited into ordinary
English) is more realistic:

* A two-dose vaccine
released in January 2021 for emergency use [eg by frontline
medical staff] with only “moderately” high 5-10%
incidence of adverse events, and effective in 60% of
cases

*A two-dose vaccine released in March
2021 [also initially for frontline emergency use] with a
lower rate of adverse events, and effective in 70% of
cases.

*A two-dose vaccine released in April
2021 under full licensing, with an “acceptable” adverse
reaction rate, and effective in 60-70% of
cases

*A one-dose vaccine released some time
afterward, with a very low rate of adverse events and
effective in up to 90% of cases

So….the Covid-19
vaccine hunt won’t have one of those Hollywood endings
where Morgan Freeman smiles wearily, switches off his Bunsen
burner and says “Problem solved, throw open the
borders!” There will be fine-tuning required.. Some
vaccines will be found to work better with fewer side
effects, depending on age, gender and ethnicity. Also,
achieving a safe and reasonably effective Covid-19 vaccine
formulation will be just the beginning. We also need to be
considering :

(a) how to manufacture or import the
vaccine under licence on a mass scale via supply chains
negotiated jointly with other countries, and/or with the
vaccine providers

(b) how to refrigerate and transport
the vaccine in a stable state for weeks in the minus 70
degree conditions that some
of the vaccine contenders currently require

and

(c) how to acquire sufficient quantities of the
medicinal glass vials and stoppers to store and administer
the vaccine safely, efficiently, and equitably.

This
likelihood that ‘first will not be best” also has
implications for political management. On recent
performance, it will be a difficult for government to
convince the media, the business sector, the Opposition and
an anxious public that waiting for a better vaccine ls
desirable – and that this delay hasn’t been due to a
government failure to win New Zealand a higher place in the
global queue. In the face of a global pandemic, preaching
the virtues of deferred gratification is going to be a hard
sell.

Small, perfectly formed vaccines

Last
Thursday, a visit to the Malaghan Centre at Victoria
University gave PM Jacinda Ardern and Research, Science and
Innovation Minister Meghan Woods an opportunity to update
themselves – and the wider public - about New Zealand’s
current state of vaccine readiness. Our vaccine preparedness
strategy was kicked off by the $37 million investment announced
in May
. The strategy is being managed by a task force
led by MBIE and the Health Ministry, and includes other
purchasing and regulatory agencies. .

On Thursday,
Ardern and MBIE‘s Dr Peter Crabtree confirmed that the
government is engaged with all of the leading vaccine
providers both directly, and through our participation in
various international and local vaccine alliances. New
Zealand is also having discussions with other countries that
are already setting up advanced purchasing arrangements with
some of the vaccine providers deemed most likely to succeed.
Ensuring supply for New Zealand will involve a degree of
piggy backing on ( and supporting) the huge pre-order
commitments that Australia, the US, the UK and Europe have
been making over the past couple of months. (There was
global pushback against early attempts by the Trump
administration to monopolise vaccine supply for
Americans.)

One aim of the early purchasing deals has
been to secure supply at an affordable price per dose The
measures in train have included:

  1. Diplomacy. On
    Thursday, Ardern mentioned that she been talking about
    vaccine prospects and access issues (including presumably, a
    consistent regulatory approach) with Angela Merkel, Justin
    Trudeau and Scott Morrison
  2. Negotiating as mentioned,
    with the pharmaceutical companies involved in vaccine
    creation and trialling and with those governments engaged in
    pre-ordering between 100 million doses from the likes of
    Astra Zeneca (as Australia has done) and the 300 million
    doses from Astra Zeneca reportedly ordered by the United
    States.
  3. Donating to the international vaccine
    distributing organisations here and abroad ( eg the GAVI Alliance) that are
    trying to establish a fair and equitable global system of
    access to Covid-19 vaccines
  4. Funding the local
    capacity for large scale vaccine manufacture and
    delivery
  5. Funding promising local vaccine makers, so
    that we can contribute to the global array of effective
    vaccines. Ultimately, there will be about 9 billion
    potential customers for such vaccines. We know already that
    infection rates and outcomes differ according to age, gender
    and ethnicity. Those variations allow for targeted vaccines
    to be developed, in accord with national characteristics. In
    the medium to long term, there looks like being plenty of
    room ( and potential for profit) for niche
    contributions.

Clearly. a small country like New
Zealand can’t afford to buy its way up the queue for a
successful Covid-19 vaccine. We can’t match the purchasing
power of the United States. Our main bargaining chip has to
be that in the context of this global pandemic, we’ve
earned a few brownie points by being a good global citizen
– as demonstrated by how we’ve contributed funds and
expertise to the international effort to combat this virus.
Here’s an update on some of the key challenges
:

1.Who are the leading contenders?
As mentioned, testing for safety and efficacy will
need to be carried out amongst human groups large enough and
diverse enough (in age, gender, and ethnicity ) to pick up
any significant side effects. For any vaccines that pass
such tests, the
initial challenge
will be to gear up the resources
required to make hundreds of millions of doses. Hopefully,
the fact there are scores of contenders at various states of
readiness will spread that effort.

The leading group
– judged by results to date, and progress towards
wide-ranging human trials are (a) the Astra Zeneca’s
vaccine being developed in conjunction with scientists at
Oxford University (b) the Moderna vaccine being developed
with the National Institute of Allergy and Infectious
Diseases (c) the Pfizer vaccine being developed with the
German firm BioNTech and (d) the Johnson and Johnson vaccine
being developed via J&J’s Janssen Pharmaceuticals
subsidiary.

2.What are the differences between
them?
The 100 or so Covid-19 vaccines in
development come in all types, and in variations within each
of those types. There are the“inactivated
virus” vaccines (eg the Johnson and Johnson effort) the
“viral vector” vaccines ( eg Astra Zeneca, which is
using a tweaked version of a chimpanzee-derived common “
adenovirus” as a delivery vehicle) and thirdly , the
“mRNA/ DNA” vaccines being pioneered by Moderna and
Pfizer.

To convey some idea of the complexity
involved…reportedly, Johnson and Johnson delivers the
SARS-CoV-2 spike protein into cells using an inactivated
common cold virus as the delivery vehicle. That prompts the
immune system to launch a counter attack against COVID-19.
J&J is currently developing seven vaccine candidates,
each of which involves the expression of a different variant
of the spike protein.

In practice, all of the various
delivery platforms share the common aim of triggering the
body’s immune system to recognise and attack any intruder
resembling the virus responsible for Covid-19 - such that
(later) when the real virus arrives, the immune system has
made antibodies ready for deployment against the intruder.
Just how enduring the protection/mitigation effects of these
antibodies will be is currently a bit of an unknown. In
recent days, there have been disturbing reports from Hong
Kong of Covid-119 re-infection occurring, only a few months
down the track. Scarily, this would suggest that the
antibodies may offer protection for only a brief period of
time. Obviously, this would limit the effectiveness of
any vaccine.

Footnote: By way
of historical comparison, Albert Sabin’s famous oral polio
vaccine of the 1950s relied on an “attenuated” virus as
a vehicle, while Jonas Salk’s polio vaccine used a
“de-activated” form of the virus. By modern standards,
both were relatively difficult to manufacture and to store
in large, stable quantities. Back then, they also carried a
(limited) risk of reverting to an active form of the
virus.

3. Is anyone potentially unable to take
the vaccines?
The Covid-19 vaccine contenders rely
on deliberately stimulating the body’s immune system to
combat the virus. This could therefore be problematic for
those with pre-existing medical conditions that require
medications that suppress the immune system. Malaghan Centre
scientists spoken to for this article confirmed that people
reliant on immunosuppressants will probably need to wait for
“ herd immunity” to develop within the wider population
at say, a 95% rate of Covid-19 vaccination. /

Advice
on the management of immunosuppressants and Covid-19
infection can
be found here
. A study in the Lancet (based on
2020 research conducted in Italy) concluded that advanced
age and pre-existing medical conditions were more
significantly linked to poor outcomes from Covid-19 than the
taking
of immunosuppressants per
se
.

4.What is the likely cost for
dose?
At this point, everyone can only speculate
about the likely costs per dose. If and when a Covid-19
vaccine arrives, it will almost certainly be restricted at
first to frontline medical staff. When made more widely
available, it could be offered free via the public health
system, as the Morrision government has already promised to
Australians, and as the Trump administration has promised to
Americans. Obviously, taxpayers will eventually be picking
up the tab for these political acts of generosity, via
taxation.

Still, the current projected costs per dose
emanating from the leading vaccine contenders do give a
useful ballpark indication for government purchasing agents,
such as Pharmac. Cost will be one factor in the access and
licensing negotiations we have with Australia – and will
also be a consideration as Canberra and Wellington construct
a vaccine supply chain within the Pacific region.

In
no particular order. Johnson and Johnson is offering its
vaccine at
$US10 a dose
within the context of a100 million dose
contract. Details of the huge pre-order deals that the US
and UK governments have made for the Pfizer/BioNTech vaccine
can
be found here
. At present, Moderna is reportedly
charging between $US32and $US37 per dose for
its candidate
. Sinopham , the state-owned Chinese
pharmaceutical company. is reportedly pitching the
cost of its vaccine
at up to $US145 for the two shots
required.

As mentioned, the Astra Zeneca vaccine is
the candidate most likely to be the first entrant in New
Zealand. Stage three trials are being conducted in Brazil,
South Africa and the United Kingdom. Australia has
(tentatively) put a 100 million dose purchase order in place
with Astra Zeneca. The 300 million dose pre-order deal that
Astra Zeneca has struck with the US government roughly
translates to a price of $US4 per dose but that estimate may
rise, given that the $1.2 billion bulk sum being cited also
includes an undisclosed figure for clinical
development.

Clearly what this underlines is that cost
control will definitely require New Zealand to attach itself
to the large pre-orders being placed by other countries. It
is doing so with Australia over access to the Astra Zeneca
vaccine, and we will presumably add our weight to
Australia’s access deals with the other contenders as
well, as these develop. On that score, it would be
interesting to know if Ardern’s recent talks with Angela
Merkel included possible access to the vaccine that Pfizer
is developing with the German firm
BioNTech.

5.Can we adequately refrigerate
these vaccines?
If we’re serious about our
Vaccine Preparedness Strategy, the plan will need to
consider how to go about creating an unbroken ‘cold
chain’ from the site of importation/manufacture right on
through to the point of vaccination. Efficient refrigeration
is going to be crucial to preserving the vaccine’s
potency, and
to avoiding wastage
: “

The World
Health Organization estimates
that up to 50% of
vaccines are wasted globally every year; a large part
because of lack of temperature control and the logistics to
support an unbroken cold-chain. At the scale of COVID-19,
this spoilage rate could waste potentially a billion
vaccines, which, even if valued at a non-profit cost of
around $10 a vaccine, represents a staggering wasted
investment.

Relevant point being, RNA is highly
unstable. So if the mRNA/DNA vaccine type proves to the
safest and most effective vaccine, the need for portable
refrigeration will become even more acute. Last Thursday I
mentioned to Malaghan Centre director Graham Le Gross, that
achieving effective refrigeration will pose a delivery
problem for the likes of Africa and India. And here as well,
Le Gros ruefully replied, given that our public health
system doesn’t have much in the way of minus 70 degree
capacity readily at hand. .

6. And what about
the medicinal glass?
We’re talking about three
hundred million Covid-19 vaccine doses for the US alone, and
between three and five million doses for New Zealanders.
Those numbers appear bound to
create a worldwide shortage of medicinal glass
, and will
compound the pre-pandemic shortage of
the silica essential to glass making
. Any Vaccine
Preparedness Strategy will require us to secure either
overseas supply (or the ability to locally manufacture ) the
glass vials and stoppers cehtral to the delivery of any
large scale vaccine programme. The risk is that medicinal
glass could become a
significant bottleneck
(no pun intended) in the global
vaccine effort. This problem can only be partially mitigated
by storing multiple vaccine doses in a single
vial.

7. What about the IP? Right
now, the global effort to combat the coronavirus has seen a
remarkable level of collegial joint effort and the free
sharing of research findings and trial outcomes. Yet at some
point, the pharmaceutical companies (and countries) engaged
in the development of new vaccines (and this includes the
re-purposing of existing patented medicines) will be looking
to recoup some of their investment. Efforts to patent and
licence Covid-19 related medical innovations seem
inevitable. The question will then arise as what parts of
the various technology platforms and gene sequencing
techniques can legitimately be patented, and on what
grounds.

If New Zealand seeks to build a capacity here
to manufacture vaccines, this would (presumably at first) be
under licence, from patent holders located elsewhere. If we
did succeed in making a significant contributions to the
development of our own Covid-19 vaccines or medical
treatments, this might well – for instance - involve the
use of genetic sequences in whole or chopped parts, derived
from humans or other primates, or created synthetically.
Given the size and value of the potential market, the legal
environment for Covid-19 vaccines and medical treatments
will encourage fierce competition. Membership of those
international vaccine alliances may offer us some protection
even if we eventually do need to amend our domestic law in
line with the rules such alliances may establish.

In
April Victoria University professor Susy Frankel ( a
property law expert) gave a brief overviews of the patent
situation with respect to pandemic medicines and vaccines.
Frankel’s contribution kicks
in around the 20 minute mark here
. As we move closer to
the specifics of what can (and cannot) be patented in the
area of genetic manipulation….it is widely agreed that
human life and genetic sequences drawn from it cannot be
patented.

To that end, the landmark 2015 case
D’Arcy v Myriad Genetics has provided a
useful preview of issues likely to resurface
with
respect to Covid-19 vaccines and treatments. Briefly,
D’Arcy argued that the isolated nucleic acids central to
Myriad’s patent were not significantly different from
cellular nucleic acid. Even in isolated form, D’Arcy
argued, naturally occurring DNA and RNA are products of
nature, and therefore cannot form the basis of a valid
patent.

Myriad responded that their unique isolating
technique had created “a new and useful effect of economic
significance, and that the isolated nucleic acid differed
from the nucleic acid found in a human cell chemically,
structurally and functionally.” Regardless, D’Arcy won,
thereby preventing private companies ( for a time at least)
from gaining a virtual monopoly on some elements derived
from human nature. Arguably, any other result could have a
serious chilling effect on research vital for public health
purposes.

Fine. But what about situations where the
material is being manufactured and manipulated by techniques
that result in synthetic outcomes that are significantly
detached from nature ? Arguably this could be the case in
the new, chopped sequences and related techniques central to
the mRNA/DNA vying as Covid-19 vaccine
contenders.

Obviously, this territory is open to
challenge. In the US case Association for Molecular
Pathology v Myriad Genetics,
the Court ruled that
synthetically created cDNA is patentable, while also
maintaining the earlier position that isolated natural DNA
is not. So far, New Zealand patent law hasn’t really had
to grapple with some of the issues inherent with the new
vaccines. It will need to do so if and when this country
embarks on building its own Covid-19 manufacturing
capability. This will be regardless of whether we import
Covid-19 vaccines under licence, or whether we create them
here via our own scientific efforts. If we do successfully
create new vaccines here, we will obviously want them to
have IP protection. Yet some such work may to some degree,
be building on existing techniques that may in future become
subject to a patent claim. There isn’t a clear road
ahead.

Footnote: If you have the time
and inclination to go down a legal rabbit hole as to how
prior patent rulings – concerning a firm called Arbutus -
have cast a patenting shadow over Moderna’s Covid-19
vaccine contender, then be
my guest.

8. Future Prospects

Finally,
what should we expect once the first Covid-19 vaccine stage
three trial results begin to emerge over the next few
months? According to the US pharmaceutical researcher and
analyst Derek Lowe we’re quite
likely to see a patchwork quilt of
results
:

What if [we have]Vaccine A being
pretty good, but not in older patients, while Vaccine B
seems better in that cohort but is harder to roll out for
distribution, while Vaccine C showed more even results over
various patient cohorts but is beaten by some other
candidate in any particular one, while Vaccine D was strong
but definitely had more adverse events. . .I can easily
imagine something like this happening, and the thing is,
it’s not just going to drop all at once. We’re going to
get those various results one after the other and will have
to fit them into an unavoidably messy picture, adjusting our
plans as more data points become available.

Right.
And will the government bow to the pressure to buy them all,
whatever the cost? Lets hope not. Lets hope we can have a
rational public debate about how best to allocate our
limited resources, in order to secure the Covid-19
vaccine(s) that offer the widest benefits to the most
people, with the fewest number of serious side effects. But
as Lowe says, “wait and see” isn’t exactly the
zeitgeist mood right
now.

© Scoop Media

 



Source link