OR WAIT null SECS
Today's reality and the hopes of tomorrow of the COVID-19 pandemic—an updated mapping of vaccines authorized by regulatory bodies and those close to it.
The joint effort of pharmaceutical companies and regulatory bodies made it possible to develop and authorize several COVID-19 vaccines within a year. A remarkable result, given the high standards of efficacy and tolerability required by regulatory authorities to grant approval, albeit conditional on future vaccine results, for their clinical use.
This article proposes an updated mapping of vaccines authorized by regulatory bodies and those close to authorization, thus offering an overview of the prevention commitment which, together with the therapeutic one based on innovative drugs (e.g., monoclonal antibodies), the scientific community is lavishing to counter the COVID-19 pandemic.
The Pfizer / BioNTech's vaccine was the first to be authorized in the US and Europe to prevent Covid-19 infection. It received emergency use authorization from the British regulatory authority (MHRA) on December 2, and from the Food and Drug Administration (FDA) on December 11. The European Medicines Agency (EMA) conditional approval came on the 21st of the same month. In all three cases, the use of the product is indicated for individuals aged 16 or over.
The vaccine, obtained using absolutely innovative technology, is based on a "messenger RNA" molecule. This molecule contains the genetic instructions cells need to "build" the spike protein of the virus external envelope and which the latter uses to penetrate inside human cells. Once released into the body, these proteins are recognized as extraneous by the immune system, which produces both anti-SARS-CoV-2 antibodies and immune cells called "T cells" capable of responding to the virus through a specific immune system's response.
Pfizer / BioNTech's vaccine has shown 95% efficacy against the virus's naive form when administered in two successive doses, the first three weeks after the second.
If it can be considered such, its limit is that the product requires a particular "cold chain" for storage and transport, assuming the use of coolers at freezing temperatures: between -112⁰F and -76⁰F.
Moderna's vaccine obtained conditional approval from EMA on January 6 and from the UK MHRA on January 8, having already received emergency use authorization from the FDA on December 18, 2020.
Like Pfizer / BioNTech's vaccine, Moderna’s uses messenger RNA technology and acts on the body with the exact mechanism of action. Its use is indicated in the population aged 18 years or older.
This vaccine has shown a very high efficacy—94.1% of the overall vaccinated population—against the virus's original form. It has also demonstrated 90.9% efficacy in participants at risk of severe COVID-19, including those with chronic lung disease, heart disease, obesity, liver disease, diabetes, or HIV infection. The efficacy remained high regardless of gender, population and ethnicity. The Moderna vaccine requires two administrations, 28 days apart from each other.
It requires a refrigerated storage and transport system, but at higher temperatures—from -13 to 5 °F for 6/7 months—than those needed for the Pfizer / BioNTech vaccine.
Compared to Pfizer / BioNTech and Moderna, the AstraZeneca / Oxford's vaccine is a "viral vector." This technology foresees not to inject mRNA but a harmless virus (a chimpanzee adenovirus) that contains a DNA sequence adequate to produce the Sars-Cov-2 spike protein.
The Lancet magazine published a preliminary analysis conducted on 11,636 participants aged 18 to 55, predominantly white (over 80%) and female (60%), of which 7,548 in the UK, 4,088 in Brazil with four months of follow-up. The results show that the vaccine guarantees 90% protection - just below Pfizer and Moderna vaccines - on this age group and an overall efficacy of 70.4%.
Conditional approval, granted by the UK MHRA on December 30 and EMA on January 29, recommends two doses, with an interval of 4 to 12 weeks between the first and second, according to the following dosage schedule: half dose at the first administration and a second full dose.
Compared to Pfizer and Moderna products, the AstraZeneca / Oxford's vaccine can be stored, transported, and handled under normal refrigerated conditions (35.6 - 46.4 °F) for at least six months. On February 9, the South African authorities had suspended the vaccine's administration following "disappointing" results in preventing contagion of the local variant but, in light of its protective effect from the most severe forms of the disease and fatal events, they are reconsidering their decision.
Although the available data seem to indicate superior efficacy for Pfizer / BioNTech and Moderna vaccines, the comparison is difficult, especially when considering the diversity of the populations studied and the need to expand the efficacy, durability and safety data of the three products in different populations of individuals.
An example of such difficulties is represented by the data from the registration studies for the AstraZeneca vaccine: they present a level of uncertainty in the estimate of efficacy in subjects over 55 years of age, as this population (in which, however, a good antibody response) was poorly represented.
In an attempt to contextualize the best conditions of use of the three vaccines and, in particular, in relation to the efficacy of the AstraZeneca vaccine on the population over 55, the AIFA Technical-Scientific Commission has suggested a preferential use:
These recommendations will have to harmonize with the organization of the vaccination campaign and the availability of individual vaccines. In this regard, it will be necessary to take into account that, at the moment, there are no reliable data on the duration of the coverage offered by the approved vaccines and that it will therefore be necessary to provide timely recall when their effectiveness will wane.
The spreading of variants of the SARS-CoV-2 virus has sparked the scientific community's debate about vaccines' efficacy against the British, South African, Brazilian, and Australian strains. According to some observers, the vaccines authorized to date are less protective against COVID-19 mutant strains.
In contrast, a pool of experts from the World Health Organization on February 10 reiterated the need to do everything possible to reduce the circulation of the virus, prevent infections and reduce the opportunities for the virus to evolve, giving rise to mutations that can potentially reduce the effectiveness of existing vaccines. The potential loss of efficacy is a cause for concern, as the most common variants among those identified so far have a higher contagiousness rate than the original virus.
In this perspective, WHO experts have stated that the AstraZeneca / Oxford vaccine can protect against severe forms of infection, against the risk of hospitalization and death. They have also confirmed the opportunity to use this vaccine in over 65, both in the contexts in which the virus's variants are circulating.
The Gamaleya Research Institute, which is part of the Russian Ministry of Health, has created a vaccine with an efficacy rate that, according to data published by The Lancet magazine on February 2, is 91.6%. Gamaleya produced the vaccine, called Sputnik V, from two adenoviruses called Ad5 and Ad26. Both types have been tested as vaccines for several years. By combining them, the Russian researchers hoped to avoid a situation where the immune system could learn to recognize the vaccine as a foreign object that needed to be destroyed.
Sputnik V, which must be stored at -0,4 °F and administered in two doses three weeks apart, is registered in 16 countries worldwide but not yet authorized in Europe or the USA.
Sinovac Biotech, a privately-held Chinese company, developed an inactivated vaccine called CoronaVac in early 2020. A year later, clinical trials in Brazil, Indonesia, and Turkey all indicated that the vaccine protected against coronavirus, with an average rate of effectiveness equal to 50.38%. Despite the absence of published data, Sinovac announced on February 6 that China had granted conditional approval for the vaccine. Other countries are also starting to use the vaccine.
The Beijing Institute for Biological Products has created the BBIBP-CorV, an inactivated vaccine against the coronavirus. It has undergone clinical trials by the Chinese state-owned company Sinopharm. On December 30, Sinopharm announced that the vaccine was 79.34% effective, prompting the Chinese government to grant it approval. The company still has to publish the detailed results of their phase III study.
Vaccines, like drugs, generally require years of research before reaching marketing authorization. The Covid-19 pandemic's emergency still represents an unprecedented challenge for science, putting enormous pressure on pharmaceutical and biotech companies to produce safe and effective coronavirus vaccines in record time. Worldwide, researchers are currently testing 69 vaccines in clinical trials on humans, and 20 have reached the final stages of development. At least 89 preclinical vaccines are being actively tested on animals.
Novavax, a US biotechnology company developing next-generation vaccines for serious infectious diseases, has recorded positive results for COVID-19 vaccine candidate NVX-CoV2373, achieving interim 89.3% efficacy in a UK Phase III study and 60% in a South Africa Phase IIb trial. These percentages would seem to indicate its efficacy even against some of the more contagious variants of the original virus.
NVX-CoV2373 differs from other already-approved COVID-19 vaccines, using novel recombinant nanoparticle technology, including a proprietary adjuvant to boost the immune response. The vaccine essentially works by "teaching" the immune system to make antibodies against the spike protein.
Also, for this vaccine in development, as for those already authorized, two doses will be necessary, the second 21 days after the first. NVX-CoV2373 should be stored frozen but can remain stable for up to three months in the refrigerator. It can be shipped and stored using standard refrigeration; this differentiates it from the Pfizer / BioNTech vaccine, which requires ultra-cold freezing conditions. From that of Moderna, which must be kept at -13 °F and 5 °F.
The vaccine under development by Janssen (J&J) is based, like AstraZeneca, on a genetically modified and defused adenovirus used as a vector. In this case, it is a human variant of the cold virus (Adenovirus Type 26-Ad26) and not chimpanzees. The use of the human variant could affect the vaccine's effectiveness, as individuals infected in the past could retain an "acquired memory" of the vector and, consequently, give rise to a less powerful antibody response.
The vaccine is still in the experimental phase; it leverages the company's AdVac platform, already used to develop and manufacture Janssen's European Commission-approved Ebola vaccine and develop its experimental Zika, RSV, and HIV vaccine candidates.
The first data indicate about 66% efficacy worldwide (72% in the USA and 54% in South Africa but towards the latest variants), with the advantage, compared to competitors, that this efficacy is achieved with a single dose.
Furthermore, like the other US candidate (Novavax), this can be transported and stored for three months at normal refrigeration temperatures (between 35.6 and 46.4 °F). The company has already started the submission procedure at EMA.
Erika Ornago is the co-founder and Pharma director of the pharmaceutical consulting firm Maxer Consulting.
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK (The Lancet, 8 December 2020)
Oxford-Astrazeneca COVID-19 vaccine efficacy (The Lancet, 8 December 2020)
Oxford University/AstraZeneca vaccine authorized by UK medicines regulator (GOV.UK, 30 December 2020)