Enhanced CPD DO C COVID-19Commentary

Lakshman Samaranayake Sukumaran Anil

Understanding COVID-19 Vaccines

As discussed in our previous article,1 the community, leading to a resumption mask-wearing and hand hygiene, for
there are a number of coronavirus of pre-COVID-19 ‘normalcy’ in the the foreseeable future. To reap optimal
disease 2019 (COVID-19) vaccines near future. In general, to reach herd benefits from vaccinations, and to reach
belonging both to the traditional, and immunity, and to suppress community the magic target levels required for
the next generation vaccine platforms, transmission of the virus, about 50–70% herd immunity, a fuller understanding
currently reaching the arms of millions of the population would have to be of how vaccinations prevent disease
in many regions of the world, from the immune to a specific virus, either is important for healthcare workers, in
UK to Brazil. Additionally, at the time of through naturally acquired immunity particular, to offer advice and guidance
writing, there were at least 10 vaccines (via asymptomatic or symptomatic to their team, the patients, as well as the
approved for early or limited use, and a infection) or artificially acquired public, as discussed below.
further 20 vaccines in large scale, Phase immunity through a successful
III, final trials.2 The vast majority of these vaccination process. For example, herd Vaccine vagaries
should see the light of day in 2021. immunity against measles requires Vaccines and vaccination procedures
A popular assumption is that approximately 95% of a population to have had their fair share of proponents
COVID-19 vaccines will provide herd or be vaccinated while the threshold for and opponents since their introduction
population immunity that can reduce polio is lower, at approximately 80%.3 some two centuries ago by Edward
transmission of severe acute respiratory The proportion of the population Jenner, in the UK, to prevent smallpox.
syndrome coronavirus 2 (SARS-CoV-2) in that must be vaccinated against SARS- This said, vaccines continue to prevent
CoV-2 to induce herd immunity is scores of bacterial and viral infections,
unknown, as yet, although experts opine while a few others such as polio
Lakshman Samaranayake, DDS, that a 60–70% immune population and smallpox have been virtually or
DSc (h.c.), FRCPath, FRACDS, FDS will stop the community spread of totally eliminated.
RCS(Edin), FDS RCPS, Professor Emeritus the disease. Considering the scientific, Clearly, vaccines are not the
(Microbiomics) and Immediate-past Dean, societal and political obstacles that need panacea for infectious disease for a
Faculty of Dentistry, The University of to be overcome to achieve this figure, it variety of issues. Whenever a new
Hong Kong, Hong Kong and Sukumaran is dawning on the scientific community vaccine, such as for COVID-19, is
Anil, MDS, PhD, FDSRCS, FDSRCPS, that COVID-19 vaccines may not be introduced, these issues resurface,
Professor & Senior Consultant, Oral Health
the panacea for this dreaded disease, leading to intense scrutiny among
Institute, Hamad Medical Corporation,
in the shorter term. As a community, health professionals as well as the
Qatar University, Doha, Qatar.
we may have to continue to resort to public. Some of these, appertaining
email: [email protected]
other protective measures, such as to vaccines in general would also be
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applicable to COVID-19, and include: and should be distinguished clear which of the available COVID-
 Vaccine-induced immunity; from binding antibodies or non- 19 vaccines provides what type of
- neutralizing versus neutralizing antibodies (nNAb). As immunity, and to what proportion of
binding antibodies; the name implies, the latter bind to vaccinees, until all the clinical trials
- effective versus the pathogen, but do not interfere are completed and mass vaccination
sterilizing immunity; with viral entry into the host cells, results are evaluated. Nevertheless,
 Vaccines and side effects; possibly because they do not bind there is hope, as there are a number
 Vaccine non-responders; to the correct region of the virus. of vaccine precedents for epidemic-
 Pre- and post-vaccination serology; However, binding antibodies play prone diseases, such as measles,
 Booster vaccinations; a contributory role in attacking the polio and hepatitis B, where the
 Vaccine hesitancy. invading virus by signalling the vaccination process does not produce
immune cells, after which the virus sterilizing immunity.
is processed and destroyed by the
Basics of how COVID-19 vaccines work recruited immune cells.4
Neutralizing antibodies, on the Vaccines and side effects
An outline of how a vaccine inhibits
natural infection is given below to other hand, can neutralize the virus Despite the availability of numerous
understand the nuances of the COVID- even without the support of other effective and efficacious vaccines
19 vaccine functionality (Figure 1). immune cells. For instance, in the over the last half a century or so,
The aim of a vaccine is to stimulate case of COVID-19, the neutralizing there is a significant proportion of the
the body’s own protective immune antibodies bind to the spike (S) population who are hesitant to take
response, mainly antibody-producing antigens on the viral surface and any vaccine (see below) due to the
B cells and the enabling T cells, so render the ‘spikes’ ineffective in side-effects of the vaccines. However,
that, if an individual encounters a attaching to the host cells, thereby the vast majority of the side effects of
specific viral pathogen, then the stopping the virus in its tracks current COVID-19 vaccines appear to
immune system can quickly recognize (Figure 1). The holy grail of the be minor with injection site pain, rash
and destroy the invading virus and vaccine manufacturers, therefore, is and soreness, to headache, muscle
terminate the disease process. For the to produce neutralizing antibodies, aches and malaise lasting 3 or 4 days.
vaccines against SARS-CoV-2, the goal rather than binding antibodies. In this context, when a vaccine
is to produce antibodies against the The currently approved COVID- is offered to a dental team member,
spike (S) protein or the proteins on the 19 vaccines are all extremely the team leader may have the
receptor binding domain (RBD) on the effective in producing these responsibility of providing information
viral surface (Figure 1). The numerous neutralizing antibodies. on the currently offered vaccine
spikes on the viral surface initiate its The neutralizing antibody response type, side effects and other relevant
attachment to susceptible human cells of an individual can also be sub- details to the prospective vaccinee in
(via the receptor binding proteins), categorized into two different types: consultation with the local medical
allowing it to enter the cell, and hijack an effective antibody response and a care provider, depending on the
the DNA of the cell to produce a viral sterilizing antibody response.5 There requirements of the local jurisdictions.
progeny that will re-infect other cells is a nuanced, but important clinical This will be a dynamic scenario that
and cause the infection. Neutralizing the difference between these, as effective needs to be astutely monitored, as
critical functionality of the protruding immunity prevents the vaccinee the database on the new vaccines,
spikes that facilitate viral entry, with the from contracting the illness and the including their side effects, is still
vaccine-induced, preformed antibodies, development of antibody-mediated rudimentary. COVID-19 vaccine side
and backed by the enabling T cells, immunity. However, the vaccinee may effects, and reports of these are
prevents the infection.1 have an asymptomatic infection and now available in real time (https://
become a silent carrier of the disease medshadow.org/covid19-vaccine-
over a period of time. Consequently, side-effects/)
Vaccine-induced immunity the vaccinee may unknowingly
Antibodies produced by the B cells of become a ‘silent spreader’ of SARS-
the immune system (Figure 1) can vary CoV-2 for an indeterminate period. Non-responders
both in quantity as well as in quality. In the case of sterilizing Some of the current next generation
In general, antibodies can be divided immunity, the very high level of mRNA vaccines have an efficiency
into two basic types: neutralizing seroconversion completely prevents approaching 95%, while this figure
(NAb), and non-neutralizing antibodies virus multiplication in a vaccinee’s cells, may be lower for other vaccines.
(nNAb). The antibodies that block and prevents the further transmission Hence, depending on the vaccine
entry of the pathogen into the of the virus to another. Sterilizing strain, a very small number of
host cells, and stop the infection, immunity is a key goal of vaccine vaccinees will not seroconvert and/or
are called neutralizing antibodies, manufacturers and it will not be develop neutralizing antibodies. It is,
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Figure 1. A highly simplified representation of how a vaccine works (as exemplified by the lipid nanoparticle mRNA vaccine for COVID-19). A. The vaccine
containing mRNA of SARS-CoV-2 with the code for either the Spike (S) protein or the receptor-binding domain (RBD) proteins, within lipid particles are
administered to the vaccinee. B. Once injected, the lipid particles are ‘ingested’ by vaccinees’ cells. The protein-making machinery in these cells is instructed
to produce viral proteins (i.e. S or RBD antigens), that are displayed on the cell surface of antigen-presenting cells (APC) (purple). C. APC then recruit T
cells (green) that are activated to kill SARS-CoV-2-infected cells (lower left panel). D. APC also recruit B cells (blue) that are primed to produce neutralizing
antibodies to the viral S and RBD proteins, preventing viral attachment to host cells and stopping the infection (lower right panel). E. Long-lived memory B
and T cells (light brown) are also produced simultaneously that can patrol the body for any incoming viruses for months/years and rekindle an identical B
and T cell response.(Image courtesy Dr Kausar Fakhruddin; software Biorender.com)

as yet, unclear how such non-responders, Pre- and post-vaccination serology individuals checked before vaccination, in
who do not develop optimal levels Once an individual consents to be the current circumstances where vaccines
of antibody, should be employed in a are reaching millions of arms worldwide, is
vaccinated, establishing the vaccinees
clinical environment. Practitioners should, a daunting prospect and appears to have
immune status is important both
therefore, be aware of this pitfall and await been disregarded for practical reasons.
guidance on these immune correlates that before, and after the single- or two-dose There are also some who argue that if a
are yet to be developed, and deal with vaccination procedure – at least in theory, person has contracted COVID-19, there is
such situations as per the stated policies in accordance with previous immunization no necessity for vaccination, pointing to
of local jurisdictions. regulatory practices. This said, having the fact that there are only a handful of
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documented re-infection reports, even vaccination by the community despite (accessed January 2021).
after 100 million cases of confirmed the availability of vaccination services.8 3. Sadarangani M. Herd immunity:
disease worldwide.6 And even among It is a complex societal problem, how does it work? Oxford Vaccine
the rare cases of re-infection, their fuelled by numerous myths, rumours
Group. 2016. https://www.ovg.
disease courses were reported to be and fears about the disadvantages
ox.ac.uk/news/herd-immunity-how-
milder, and without hospitalization. Pre- of vaccines, not least because of the
does-it-work (accessed January
immunization serology testing for those associated media hyperbole and
2021).
who recently contracted COVID-19 hype. Maintaining public confidence
in COVID-19 vaccines, and increasing 4. Schmaljohn AL. Protective antiviral
appears to be a contentious issue that
vaccine uptake and minimizing vaccine antibodies that lack neutralizing
needs to be resolved in earnest.
On the other hand, it is highly likely hesitancy will be crucial to eradicate activity: precedents and evolution
that post-vaccination serology testing the disease. Dental practitioners can of concepts. Curr HIV Res 2013; 11:
would be required for dental care play a key contributory role here by 345–53. https://doi.org/10.2174/157
professionals because they appear to educating their patients and the public 0162x113116660057.
be at significant risk for COVID-19 by on the myths and the truths of COVID- 5. Kumar R, Qureshi H, Deshpande S,
virtue of their work environment, where 19 vaccines. Certainly, this task will be Bhattacharya J. Broadly neutralizing
many aerosol generating procedures much easier when there is firm data antibodies in HIV-1 treatment
are undertaken on a daily basis.7 Post- on vaccine side-effects in the fullness and prevention. Ther Adv Vaccines
vaccination serology is usually performed of time. Immunother 2018; 6: 61–68. https://.
by measuring the antibody titre 4–8 10.1177/2515135518800689.
weeks after the second dose (e.g. 6. Ledford H What the immune
hepatitis B vaccinations). It would also be Conclusions
response to the coronavirus says
reassuring to know the post-vaccination The foregoing commentary exposes
about the prospects for a vaccine.
antibody status of a vaccinee to ensure the complex, multi-dimensionality of
Nature 2020; 585: 20–21. https://
that they do not belong to the small COVID-19 vaccines which, clearly, will
minority of non-responders (e.g. 5–10% doi.org/10.1038/d41586-020-
be the latest addition to the infection
for mRNA vaccines). 02400-7.
control armamentarium of dental
professionals. The notion that the 7. Samaranayake L. Essential
vaccines and vaccine-induced herd Microbiology for Dentistry. 5th edn.
Booster vaccinations
immunity will be a panacea ushering Edinburgh: Elsevier, 2018.
It is also unclear, as yet, whether
a new dawn of pre-COVID-19 dental 8. MacDonald NE. Vaccine hesitancy:
booster doses are necessary for the
practice needs to be tempered by definition, scope and determinants.
COVID-19 vaccines after the initial
two-dose vaccine, and if so, how often the realization of a yet unfolding and Vaccine 2015; 33: 4161–4164.
these should be administered. A good volatile viral ecosystem where the only https://doi.org/10.1016/j.
example is the influenza vaccine, predictability is the unpredictability of vaccine.2015.04.036.
which requires annual boosting the disease itself.
to maintain seropositivity for the
prevalent sub-type of the virus. It may Acknowledgement
be that the regularity and frequency of The authors are grateful to Dr Kausar
the antigenic shifts we are witnessing Fakhruddin of the University of Sharjah,
CPD ANSWERS
in SARS-CoV-2, with the arrival of UAE for providing Figure 1. December 2020
various ‘viral variants’, will necessitate
an annual vaccine boost either for Compliance with Ethical Standards
the old strain of the virus or a newly Conflict of Interest: The authors declare 1. C 6. C
circulating variant. that they have no conflict of interest.

Vaccine hesitancy 2. A 7. A
Although not strictly falling under References
the remit of the clinical responsibility 1. Samaranayake L, Fakhruddin KS.
3. D 8. B
of the dental professionals, the issue COVID-19 vaccines and dentistry.
of vaccine hesitancy by the public Dentl Update 2021; 48: 76–81.
is a contentious issue that requires 2. New York Times. Coronavirus- 4. B 9. A
informed discussion and debate vaccine-tracker. Available at:
among the profession and the public. https://www.nytimes.com/
Vaccine hesitancy is defined as interactive/2020/science/ 5. B 10. B
a delay in acceptance, or refusal, of coronavirus-vaccine-tracker.html
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