Covid-19 – Vaccines options available: how to choose?

by Antonino Napoleone, Giuseppe Scarlata | March 07, 2021.

The anti-SARS-CoV-2 vaccination campaign is progressing at various levels and speeds across Europe. Several weeks have passed since 27 December 2020, known as Vaccine Day, and several weeks are expected to pass before the first results could be seen in terms of effectiveness and widespread protection among the population. The administration of the new vaccines and the effect the vaccination campaign may have on the population will only be seen over time by monitoring the immune protection induced over the spread of the virus and the consequences on those at higher risk to get serious and/or fatal disease.
The gravity of the health situation caused by the rapid spread of the virus worldwide in less than a year has generated general alarm in the scientific community, leading to rapid responses and solutions with the development of numerous candidate vaccines against SARS-CoV-2, three of which have now been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (read more: approaches and technologies adopted to develop anti-SARS-CoV-2 vaccines). As soon as phase 3 of clinical trials were completed, the pharmaceutical companies submitted the data and results to both the FDA and EMA, which in these case could make one of the following decisions after a thorough evaluation:

• Refuse authorization to the market, due to reduced efficacy or due to adverse effects that are more or less severe than the benefits provided;
• Approve the authorisation to market;
• Request further studies on doubtful or unclear aspects, to reconsider the vaccine with the new data and/or additional studies;
• Grant the Emergency Use Authorization (EUA).

Emergency Use Authorization (EUA) is a mechanism that streamlines the bureaucratic process and speeds up the availability and use of medical/pharmaceutical countermeasures, including vaccines, during a major health emergency. This regulatory mechanism applies only and exclusively in cases of emergency, provided that the strict criteria related to safety and efficacy data submitted by pharmaceutical companies upon completion of their clinical trials are fulfilled. The doubt that the anti-SARS-CoV-2 vaccines are not rigorously tested according to the designated timelines and safety criteria does not subsist in any way, because otherwise, no regulatory agency could ever provide any market authorisation.

Which anti-SARS-CoV-2 vaccines are commercially available today?

Since the beginning of the pandemic, more than two hundred research projects aimed at developing a vaccine against Coronavirus have been registered, but to date only three vaccines have successfully completed phase 3 clinical trials, meeting the safety and efficacy criteria required for marketing authorisation (EUA in these case) by the FDA and EMA. Other candidate vaccines are in the pipeline, and could probably soon join the three already approved and increase the tools available to fight the pandemic. But going back to the currently commercially available vaccines, questions arise as to what differences there are among the three approved vaccines and which of those three could be more effective in the long run? Which technological platform did they use to develop the vaccine? (read more: What is the secret ingredient in the Pfizer and Moderna vaccines?) Moreover, why should a vaccination campaign include several vaccines, and which categories of people will have access to doses of one specific vaccine rather than another? It is therefore important to analyse the pharmaceutical characteristics, methods of administration, storage and level of efficacy, in order to understand their advantages and disadvantages, but above all, how will the categories of the population receiving the vaccine be divided?

PFIZER/BIONTECH VACCINE

Vaccine name: Comirnaty.
Manufacturer: Pfizer in collaboration with BioNTech.
Vaccine type: Vaccine with mRNA (messenger RNA) molecules encoding the viral Spike protein (S protein, Figure 1) of SARS-CoV-2, embedded in lipid nanoparticles.
Efficacy: 94.6% as of 7 days after administration of the second dose.
Date of marketing authorisation in Europe: 21 December 2020.
Date of the marketing authorisation in Italy: 22 December 2020.
Method of administration: two injections, usually into the muscle of the upper arm, at least 21 days after the first injection. Once the first dose of Comirnaty has been received, a second dose of the same vaccine should follow. No data are available and it is not recommended to receive doses of another vaccine to complete the vaccination cycle.
Storage: In the freezer at -80°C (-60°C to -90°C) in the original packaging. Stable for a few hours at room temperature, just before administration.
Date of the first dose administered: 27 December 2020.
Adverse effects: Hypersensitivity to the Active Principle or to any of the vaccine excipients listed in the pharmaceutical product information¹. Cases of anaphylaxis have been reported. Appropriate anti-anaphylaxis treatment and medical care should always be immediately available in the event of an anaphylactic reaction occurring following administration of the vaccine. Note: The vaccine is administered to adults and adolescents aged 16 years and over. The safety and efficacy of the Comirnaty vaccine in the paediatric population (children and adolescents below 16) have not yet been established and the available data are still limited. Data on the use of Comirnaty in pregnant women are limited. Animal studies do not indicate direct or indirect adverse effects on pregnancy, embryonic/fetal development, parturition or postnatal development. Administration of Comirnaty during pregnancy should be considered only if the potential benefits outweigh the potential risks to the mother and foetus. Animal studies do not indicate any direct or indirect harmful effects of reproductive toxicity.

MODERNA VACCINE

Name: Moderna COVID-19 Vaccine (mRNA1273).
Manufacturer: Moderna Biotech
Vaccine type: Vaccine with mRNA (messenger RNA) molecules encoding the viral Spike protein (S protein, Figure 1) of SARS-CoV-2, embedded in lipid nanoparticles.
Efficacy: 93.6% as of 14 days after administration of the second dose.
Date of marketing authorisation in Europe: 6 January 2021.
Date of the marketing authorisation in Italy: 7 January 2021.
Method of administration: two injections, usually into the muscle of the upper arm, at least 28 days from the first injection. Once the first dose of the Moderna vaccine has been received, a second dose of the same vaccine should follow. No data are available and it is not recommended to receive doses of another vaccine to complete the vaccination cycle.
Storage: in the freezer at a temperature between -25°C and -15°C. Stable between +2°C and +8°C for 30 days if unopened.
Date of the first dose administered: 14 January 2021.
Adverse effects: Hypersensitivity to the Active Principle or to any of the vaccine excipients listed in the pharmaceutical information of the product². Cases of anaphylaxis have been reported. Appropriate anti-anaphylaxis treatment and medical care should always be immediately available in the event of an anaphylactic reaction occurring following administration of the vaccine.
Note: Moderna vaccine is administered to adults and adolescents aged 18 years or older. The safety and efficacy of the Moderna vaccine in the paediatric population (children and adolescents below 18) have not yet been established and the available data are still limited. Data on the use of the Moderna vaccine in pregnant women are limited. Animal studies do not indicate any direct or indirect adverse effects on pregnancy, embryonic/fetal development, parturition or postnatal development. The administration of the Moderna vaccine during pregnancy should only be considered if the potential benefits outweigh the potential risks to the mother and foetus. Animal studies do not indicate any direct or indirect harmful effects of reproductive toxicity.

ASTRAZENECA VACCINE

Name: AstraZeneca Vaccine
Manufacturer: AstraZeneca in collaboration with Oxford University.
Vaccine type: Viral vector vaccine using a modified version of the chimpanzee adenovirus, no longer able to replicate, as a vector to provide instructions for the synthesis of the SARS-CoV-2 spike protein (S protein, Figure 1), produced in genetically modified human cells (HEK293 cells) using recombinant DNA technology.
Efficacy: 59.5% as of 15 days after administration of the second dose.
Date of consent for placing on the market in Europe: 29 January 2021.
Date of the marketing authorisation in Italy: 30 January 2021.
Method of administration: two injections, usually into the muscle of the upper arm, at least 4-12 weeks (28 to 84 days) after the first injection. Once the first dose of the AstraZeneca vaccine has been received, a second dose of the same vaccine should follow. No data are available and it is not recommended to receive doses of another vaccine to complete the vaccination cycle.
Storage: Refrigerated at 2°C to 8°C; do not freeze.
Date of the first dose administered: the first doses will be administered in the next few weeks in Europe.
Adverse effects: Hypersensitivity to the active substance or to any of the vaccine excipients listed in the pharmaceutical information of the product³. Appropriate supervision and medical care should always be readily available in case of an anaphylactic event following the administration of the vaccine. Careful observation for at least 15 minutes after vaccination is recommended. Persons who experienced anaphylaxis to the first dose of the AstraZeneca vaccine should not be given the second dose.
Note: the AstraZeneca Vaccine is administered to people aged 18-65 years, except for the extremely vulnerable categories. The safety and efficacy of the AstraZeneca vaccine in the paediatric population (children and adolescents below 18) have not yet been established and there are no data available. The efficacy, safety and immunogenicity of the vaccine have not been evaluated in immunocompromised subjects, including those receiving immunosuppressive therapy. There is limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women. Animal studies do not indicate direct or indirect harmful effects of reproductive toxicity.

Considerations on target groups for SARS-CoV-2 vaccination

The strategic plan adopted by Italy and the EU member countries is based on and takes into account mainly the international and European data and recommendations provided by the FDA and the EMA. The recommendations on the target groups to be vaccinated will be updated on the basis of the constant monitoring and progressive evolution of the available data, in particular regarding the efficacy and safety of the available vaccines in different age groups and in different subjects considered extremely vulnerable. By ‘extremely vulnerable‘, we refer to individuals with conditions that due to pre-existing organ damage (respiratory and cardiovascular diseases, diabetes, liver and kidney diseases), or due to an impaired immune response (autoimmune diseases and immunodeficiencies, Down’s syndrome), have a particularly high risk of developing severe or fatal forms of COVID-19.
As of today, the national regulatory agencies of the European Community member states have approved the three vaccines with appropriate measures, following the EMA recommendations. In particular, the Italian Medicines Agency (AIFA), due to the more robust scientific evidence of efficacy, has suggested a preferential use of mRNA vaccines (Pfizer/BioNTech vaccine and Moderna vaccine) in the elderly and/or in the people at higher risk of developing severe or fatal forms of the disease, while the indication for the AstraZeneca vaccine remains preferential for the population between 18 and 55 years of age without severe pathologies, for which more robust data are available.

Conclusions

The vaccination campaign has begun, and expectations are high among the population, along with the desire for the first results to be tangible and help to normalise social habits as soon as possible. Studies and monitoring are still ongoing, especially to shed light on all the questions that have not been fully resolved behind the immune response triggered and the duration of protection offered by the vaccine. Moreover, the virus’ ability to generate mutant strains capable of evading the immune response should not be underestimated (read more: dynamics between immune protection and virus evolution). In a short time, scientific research has set up technological platforms capable of developing vaccines whose effectiveness and safety have been proven. At this stage, it is essential to focus our efforts over the coming months and to persevere with the production and distribution of doses as quickly as possible among the population, especially to the most vulnerable groups. Share faith in medical science rather than the media, to stop all this, it is necessary to show the arm, bear the prick of the syringe, and wait for the immune defences to do the rest.

References:

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