© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
EDITORIAL
Can COVID-19 vaccines stop the pandemic?
CS Lau, MD, FHKAM (Medicine)
Department of Medicine, The University of Hong Kong, Hong Kong
Corresponding author: Prof CS Lau (cslau@hku.hk)
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Herd immunity is needed to combat the coronavirus
disease 2019 (COVID-19) pandemic. To achieve
this, a large proportion of the population must
acquire immunisation against severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2),
to protect non-vaccinated, immunologically naïve,
and immunocompromised individuals.1 2 The cost of
achieving herd immunity through natural infection
by SARS-CoV-2 is unacceptable, as millions of
people will succumb to the disease. Therefore, a
mass vaccination campaign represents the best
countermeasure to reduce the burden of COVID-19
and allow the world to return to normalcy.
Historically, the development of an effective
vaccine took years. For example, even the measles
vaccine which was found relatively rapidly took
10 years from the discovery of the pathogen to the
development of the first vaccine.3 With COVID-19
vaccines, the world has witnessed extraordinary
progress in just 1 year. As of 2 April 2021, the World
Health Organization (WHO) has documented 269
COVID-19 vaccine candidates, with 85 of them
in clinical evaluation.4 Among these candidates,
nine different vaccines across three platforms—inactivated viral, adenoviral vector-based DNA, and
nucleoside modified mRNA—have been approved
for emergency use in 166 countries, areas, or
territories. Typically, vulnerable populations, as
well as frontline healthcare workers, are the highest
priority for vaccination.5 Almost all COVID-19
candidate vaccines target the spike protein—comprising a membrane-distal S1 subunit and a
membrane-proximal S2 subunit—that exists in the
virus envelope as a homotrimer.
An ideal vaccine should be one that is safe;
induces robust immunity and is efficacious in the
prevention of infection, symptomatic disease,
complications, and transmission; is of high quality;
and is stable and easy to distribute, store, and handle
for mass administration. The WHO has proposed
a number of minimally acceptable attributes and
criteria for considerations for the evaluation and
prioritisation of COVID-19 vaccines for further
development by developers, manufacturers,
regulators and funding agencies. Although not all of
the nine vaccines currently in use have been enlisted
by WHO for emergency use,6 all have been evaluated
by respective local ministries of health or equivalent
agencies and deemed to be safe, efficacious, and of
good quality.
In Hong Kong, an inactivated virus vaccine
(CoronaVac; Sinovac, China) and an mRNA-based
vaccine (Comirnaty; BioNTech, Germany) have been
available since the end of February 2021. Although
the arrival of COVID-19 vaccines in the city was
keenly anticipated, the vaccination rate has been less
than desirable thus far. In the first month of the city’s
vaccination programme, 6.4% of the total population
received a first dose of either vaccine.7
For any mass vaccination programmes to
be successful, public confidence, which is often
undermined by concerns over vaccine safety, is
of utmost importance. Regardless of the speed of
development of the various COVID-19 vaccines,
some adverse events are to be expected. Fortunately,
immune-mediated events, such as anaphylaxis, Bell’s
palsy, Guillain–Barré syndrome, and transverse
myelitis, have been rarely reported so far in association
with COVID-19 vaccines. However, with millions, if
not billions, of people in the world expected to be
exposed to new COVID-19 vaccines in the near future,
different strategies must be deployed to systematically
monitor the safety profiles of these vaccines. These
strategies include detailed analysis of the safety data
of phase I, II, and III clinical trials; regular mandatory
post-marketing survey studies to be conducted by the
developers; and voluntary reporting by vaccinated
subjects and their clinicians. On a public health level,
national reporting systems such as the Medicines and
Healthcare products Regulatory Agency in the UK
and the Vaccine Adverse Event Reporting System in
the US are designed to detect early safety problems
for licensed vaccines.8 Locally, the Department of
Health operates a drug safety alert system to capture
adverse events following immunisation from the
city’s medical practitioners, as well as the Hospital
Authority and other health agencies. In addition,
the Government has commissioned the University
of Hong Kong to conduct a prospective surveillance
study on adverse events of special interest following
vaccination. These data should be regularly reviewed
scientifically, and revealed to the public in an open
and timely manner to reassure the public of the
robust oversight.
On vaccine efficacy, the WHO suggested that
a minimum criterion for any acceptable COVID-19
candidate vaccines should be a clear demonstration
of at least 50% point estimate “against disease, severe
disease, and/or shedding/transmission endpoints”
on a population basis in placebo-controlled efficacy trials.9 One common misconception that many
readers have when interpreting clinical trial reports
concerning COVID-19 vaccine efficacies is that
these figures could be compared across studies.
This is incorrect as there have been no head-to-head
studies comparing two or more COVID-19
vaccines. In addition, the various phase III studies
reported so far have been conducted in different
countries where the COVID-19 situation may vary
significantly, involved different study subject groups
and employed variable efficacy endpoints, including
different clinical and molecular diagnostic criteria
for COVID-19 and its severity. Finally, there are
no standardised assays for the measurement of
SARS-CoV-2 neutralising antibodies which are a key
determinant of a vaccine’s protection rate.
Observations made in countries with
aggressive vaccination policies suggest that mass
vaccination is probably effective in controlling
COVID-19. Since December 2020, countries such as
Israel, the UK, and the US have launched progressive
campaigns to vaccinate most of their populations.
By the beginning of April 2021, over 60%, 46%, and
31% of the populations of Israel, the UK, and the
US, respectively, have received at least one dose
of COVID-19 vaccine. Israel has been particularly
aggressive with over 55% of the population fully
vaccinated.5 Encouragingly, all three countries have
seen a significant drop in the bi-weekly confirmed
COVID-19 cases per million people since mid-January (Israel: 94%; UK: 92%; US: 73%) and bi-weekly
confirmed COVID-19 deaths per million people
since the end of January (Israel: 88%; UK: 95%; US:
72%).10 It should be noted that these countries have
continued strict non-pharmaceutical interventions
including various social distancing policies. Together
with a mass vaccination programme, it seems
possible to curb the advancement of COVID-19.
So, can vaccination stop the COVID-19
pandemic? This is possible but it will likely take a
long time. Worldwide, unfortunately, only 4.7% of
the population have been administered at least one
dose of any COVID-19 vaccines so far.5 Although
the industry has ramped up its efforts in research
and development of COVID-19 vaccines, there are
too few manufacturers. The increasing production in
countries such as Brazil, China, India, and Indonesia
may fill the gap but the solution to supply shortage is
not yet clear. Coupled with the high cost of vaccines,
it is difficult to see how demand could be satisfied or
access provided to developing countries, in particular,
in the near future. Hong Kong is blessed to have had
15 million doses of vaccines procured for the people
so far. It is upon us to get ourselves vaccinated instead
of depending on herd immunity. Concerns for vaccine
safety and efficacy are understandable but that these
are closely monitored locally and internationally,
and every effort is being made to reduce vaccine-associated
reactions to a minimum. Novel vaccines
such as the adenoviral vector and mRNA-based vaccines have their overall effectiveness and safety
continuously and carefully monitored.
It is not yet known what proportion of the
population we need to vaccinate to achieve herd
immunity against COVID-19. A threshold value
of ~67% will be needed assuming that the basic
reproductive number (R0) of the virus is 3.1 2 Unless,
and until, we reach this threshold, we will not be
certain of protection against the epidemic locally
and around the world. This also needs to be achieved
as quickly as possible with the emergence of
SARS-CoV-2 variants which may be resistant to
existing vaccines rendering them less efficacious.11
“With a fast moving pandemic, no one is safe,
unless everyone is safe”.11
Author contributions
The author contributed to the editorial, approved the final
version for publication, and takes responsibility for its
accuracy and integrity.
Disclosures
CS Lau is the convener of the Advisory Panel on COVID-19
Vaccines for the Hong Kong SAR Government.
References
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Clin Immunol 2018;142:64-6. Crossref
2. Randolph HE, Barreiro LB. Herd immunity: understanding COVID-19. Immunity 2020;52:731-41. Crossref
3. Plotkin SA. Vaccines: past, present and future. Nat Med 2005;11(4 Suppl):S5-11. Crossref
4. World Health Organization. Draft landscape and tracker
of COVID-19 candidate vaccines. Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. Accessed 5 Apr 2021.
5. Our World in Data. Coronavirus (COVID-19) vaccinations.
Available from: https://ourworldindata.org/covid-vaccinations#vaccine-development-vaccines-approved-for-use-and-in-clinical-trials. Accessed 5 Apr 2021.
6. World Health Organization. Status of COVID-19 vaccines
within WHO EUL/PQ evaluation process. Available from: ttps://extranet.who.int/pqweb/sites/default/files/documents/Status_COVID_VAX_01April2021.pdf.Accessed 5 Apr 2021.
7. Department of Health, Hong Kong SAR Government.
COVID-19 Vaccination Programme: vaccination dashboard. Available from: https://www.covidvaccine.gov.hk/en/dashboard. Accessed 5 Apr 2021.
8. Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Engl J Med 2021;384:643-9. Crossref
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int/publications/m/item/who-target-product-profiles-for-covid-19-vaccines. Accessed 5 Apr 2021.
10. Our World in Data. Coronavirus pandemic
(COVID-19). Available from: https://ourworldindata.org/coronavirus#coronavirus-country-profiles. Accessed 5 Apr 2021.
11. World Health Organization. COVAX. Working for global equitable access to COVID-19 vaccines. Available from: https://www.who.int/initiatives/act-accelerator/covax. Accessed 5 Apr 2021.