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, Infectious Diseases Now 51 (2021) 319–333
Available online at
ScienceDirect
www.sciencedirect.com
Review
COVID-19 vaccines: Frequently asked questions and updated answers
M. Lefebvre a,∗ , N. Vignier b,c,i , B. Pitard d , E. Botelho-Nevers e,f , B. Wyplosz j , R. Cohen g ,
O. Epaulard h , the SPILF Vaccination Prevention group1
a
Service des maladies infectieuses et tropicales, centre de prévention des maladies infectieuses et transmissibles, centre hospitalo-universitaire Hôtel-Dieu,
Inserm CIC1413, 1, place Alexis-Ricordeau, 44000 Nantes, France
b
Centre d’investigation clinique Antilles Guyane, CIC Inserm 1424, DRISP, centre hospitalier Andrée-Rosemon, Cayenne, French Guyana
c
Inserm, Sorbonne université, institut Pierre-Louis d’épidémiologie et de santé publique, IPLESP, 75012 Paris, France
d
Université de Nantes, CNRS ERL6001, Inserm 1232, CRCINA, Nantes, France
e
Service d’infectiologie, centre hospitalo-universitaire de Saint-Étienne, CIC 1408 Inserm, 42055 Saint-Étienne, France
f
Centre international de recherche en infectiologie (CIRI), Team GIMAP, université Lyon, université Jean-Monnet, université Claude-Bernard Lyon 1, Inserm,
U1111, CNRS, UMR530, 42023 Saint-Étienne, France
g
InfoVac, centre hospitalier intercommunal de Créteil, service de pédiatrie, 40, avenue de Verdun, 94000 Créteil, France
h
Service des maladies infectieuses, centre hospitalo-universitaire Grenoble Alpes, Grenoble, France, CIC 1406 Inserm, Grenoble, France
i
Department of infectious disease, Groupe hospitalier Sud Ile-de-France, 77000 Melun, France
j
Service des maladies infectieuses et tropicales, Assistance publique-hôpitaux de Paris, Centre hospitalier universitaire Bicêtre, Paris, France
a r t i c l e i n f o a b s t r a c t
Article history: At the end of December 2019, China notified the World Health Organization about a viral pneumonia
Received 14 February 2021 epidemic soon to be named COVID-19, of which the infectious agent, SARS-CoV-2, was rapidly identified.
Accepted 23 February 2021 Less than one year later, published phase 3 clinical trials underlined the effectiveness of vaccines utilizing
Available online 27 February 2021
hitherto unusual technology consisting in injection of the messenger RNA (m-RNA) of a viral protein. In
the meantime, numerous clinical trials had failed to identify a maximally effective antiviral treatment,
and mass vaccination came to be considered as the strategy most likely to put an end to the pandemic. The
objective of this text is to address and hopefully answer the questions being put forward by healthcare
professionals on the different anti-SARS-CoV-2 vaccines as regards their development, their modes of
action, their effectiveness, their limits, and their utilization in different situations; we are proposing a
report on both today’s state of knowledge, and the 14 February 2021 recommendations of the French
health authorities.
1. Introduction vaccination campaign. Given the existing demand for simple and
objective elucidation of the available data, the French Infectious
Whereas the COVID-19 pandemic has occasioned over 100 Diseases Society (SPILF) was asked to draw up an informative sum-
million cases and more than 2.3 million deaths worldwide, the mary document to be addressed to healthcare professionals.
published results of pivotal trials of the first COVID-19 candidate
vaccines have represented a source of genuine hope for the inter- 2. Methodology
national community. Numerous countries have rapidly initiated
a COVID-19 vaccination campaign; as of 12 February 2021, more A working group proceeding under the supervision of the
than 150 million doses had been administered throughout the SPILF Vaccination-Prevention group identified the questions most
world (https://ourworldindata.org/covid-vaccinations). Numerous frequently put forward by healthcare professionals. As regards
questions have been raised in France, not only by public health each question, the literature was analyzed in view of providing a
decision-makers, but also and especially by caregivers and prac- response based on the most recent data, while remaining within
titioners in charge of informing the population, of defining and the limits of the knowledge amassed at the date of writing, and
identifying prioritized individuals, and of setting up a nationwide taking into full account the volume of continuing uncertainties. Sev-
eral experts in vaccinology, infectious diseases and/or immunology
were contacted and asked to reread and/or to participate in the
drafting of responses. Given:
∗ Corresponding author.
E-mail address: maeva.lefebvre@chu-nantes.fr (M. Lefebvre).
1
• the fact that questions are numerous;
The members of the SPILF Vaccination Prevention group are listed at the end of
the article. • the plethoric and rapidly evolving nature of available data;
https://doi.org/10.1016/j.idnow.2021.02.007
2666-9919/© 2021 Elsevier Masson SAS. All rights reserved.
, M. Lefebvre, N. Vignier, B. Pitard et al. Infectious Diseases Now 51 (2021) 319–333
• stakeholders’ expressed need for immediately enlightening infor- developed by Janssen Vaccines & Prevention (Johnson & John-
mation, a methodology premised on systematic review of the son) [Ad26.COV2.S] and the protein vaccine developed by Novavax
literature was not applied. [NVX-CoV2373].
A progress report on the preclinical and clinical development of
The present document may consequently be viewed as expert the different candidate vaccines is updated weekly on the World
opinion based on the elements at our disposal at a given point in Health Organization (WHO) website [5].
time.
3.3. Do the vaccines contain adjuvants?
3. Generalities
If live vaccines, RNA vaccines and viral vector vaccines do not
3.1. What is the antigen targeted by Coronavirus disease 2019 contain adjuvants, this is due to the fact that by their very nature,
(COVID-19) vaccines? they can satisfactorily stimulate the innate immune system. On
the contrary, inactivated vaccines and protein vaccines necessitate
The majority of the vaccines being developed target the spike adjuvants. Some of the COVID-19 vaccines now being developed
(S) protein of the virus, which is located at the surface of the contain aluminum or a number of other currently or soon-to-be
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) commercialized adjuvants, orienting helper T lymphocytes toward
envelope, enabling the latter to be bound to a cell receptor, the TH1 polarization.
angiotensin-converting enzyme 2 (ACE-2, which is present in pneu-
mocytes, enterocytes. . .) and enter into host cells; its contribution 3.4. Why did one year suffice for COVID-19 vaccines to be
to infection is consequently central. Different studies have shown developed and receive conditional market authorization?
that were neutralizing antibodies to be triggered against the S pro-
tein, protection from infection would be afforded [1,2]; that is why 3.4.1. Because the causative agent was rapidly characterized, and
spike protein represents the target of most of the vaccines devel- was found to be relatively stable
oped in 2020. On 9 January 2020, the Chinese health authorities and the WHO
announced the discovery of new coronavirus, which was promptly
3.2. What are the different types of COVID-19 vaccines? termed 2019-nCoV and presented as the agent responsible for the
pneumonia cases of which the WHO had been apprised by China on
Different vaccinal technologies, also known as platforms, are 31 December 2019. As early as 10 January 2020, the complete viral
currently being applied; they can be divided into two categories sequence was rendered public. Even though it is indeed an RNA
[3,4]. virus, SARS-CoV-2 is more stable than, for example, the influenza
or the HIV virus. That is why the vaccines developed from viral
3.2.1. Vaccines based on the whole virus sequences isolated in January 2020 were still valid in December
They may consist in a whole virus (in this case, SARS-CoV- 2020.
2), inactivated by beta-propiolactone (example: the vaccines
developed by Sinovac [Coronavac] and Sinopharm [Chinese-WIBP- 3.4.2. Because knowledge on coronavirus immunity was already
Vero-Inactivated-Covid], by Valneva [VLA 2001], and by Bharat present
Biotech [Covaxin, BBV152]) or in a live but attenuated virus (exam- Coronavirus immunity had been widely studied on the occasion
ple: the vaccine developed by Codegenix/serum institute of India of the alerts that occurred in 2002–2003 (emergence of SARS-CoV
[COVI-VAC]). in China) and 2012 (emergence of MERS-CoV in Saudi Arabia). Ani-
mal models had been developed and phase 1 clinical trials of a
3.2.2. Vaccines based on a viral protein (here, the S protein) or on DNA vaccine encoding the S protein of these two coronaviruses had
part of the protein highlighted the presence of neutralizing antibodies in vaccinated
They comprise protein or virus-like particle vaccines (molec- volunteers [6,7]. It was shown that the triggering of a response
ular S-protein aggregates), nucleic acid vaccines and viral vector against S protein or the injection of neutralizing antibodies pro-
vaccines. vided protection against the infection [1,2].
Some of them are based on a non-modified protein in whole Using the published sequence of the SARS-CoV-2 genome, in
or in part, for example the viral vector vaccines developed by the a few days it was possible on the basis of DNA synthesis to pro-
University of Oxford-AstraZeneca [AZD1222, ChAdOx1-nCoV-19] duce m-RNA corresponding to S protein stabilized in a prefusion
and by the Gamaleya Research Institute [Gam-COVID-Vac, known conformation by two proline residues at the site of the cleavage
as Sputnik V], the messenger RNA (m-RNA) vaccine developed between subunits S1 and S2, in a manner particularly propitious to
by CureVac-GSK [CVnCoV] and the protein vaccines elaborated the induction of neutralizing antibodies. The abbreviated duration
by COVAXX [UB-612], by Medicago [CoVLP], by Clover Bio- thereby obtained is in no way comparable to the time lapse needed
pharmaceuticals/GSK/Dynavax and by Sanofi Pasteur-GSK. While for the protein proteins or the virus culture required in the context
MSD drew up two replication-competent viral vector vaccines of classical vaccinal platforms.
based on the measles virus and the vesicular stomatitis virus, By chance, rapidly conducted animal trials confirmed how
their immunogenicity was deemed insufficient, as a result of simple it was to trigger an effective immune response against SARS-
which, their clinical development was suspended in late Jan- CoV-2.
uary.
The other types of vaccines are based on the modified protein 3.4.3. Because previous, highly advanced research rendered
in its prefusion form, for example the m-RNA vaccines developed possible the use of innovative vaccinal platforms
by Moderna [Moderna COVID-19 Vaccine® , mRNA-1273] and by Well before the COVID-19 pandemic, nucleic acid and viral vec-
Pfizer-BioNTech [Comirnaty® , BNT162b2], the viral vector vaccine tor vaccine platforms had been widely utilized in studies with
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