In January 2021 two more vaccines against Covid-19 disease have been approved, offering two more weapons in the fight against this pandemic. The two recently approved vaccines are the mRNA-1273 vaccine, developed by the company Moderna –together with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID)–, and the ChAdOx1 nCoV-19 vaccine (AZD1222) developed by Oxford University together with Astra Zeneca.
What are the available scientific data?
mRNA-1273 vaccine (Moderna/NIAID). The mRNA-1273 vaccine is a lipid-nanoparticle-encapsulated mRNA vaccine, meaning that similar to the BioNTech/Pfizer-developed vaccine, is constituted by an RNA molecule coding for the SARS-CoV2 Spike protein in the pre-fusion conformation1, embedded in a lipid particle. The vaccine was previously demonstrated to be effective in animal experiments2. The trial was conducted between July and October 2020 and enrolled a total of 30.420 participants. Participants were randomly assigned to receive either two doses of the vaccine (15.210 participants) or a placebo (a saline solution). Mean age of the participants was 51 years old (47,3% were female). 24,8% of participants were aged 65 years or older.
The two doses of the vaccine were administered via intramuscular injection, 28 days apart.
Safety. Overall, local reactions were mild. Moderate-to-severe systemic reactions were reported by about 50% of vaccinated participants after the second dose and included fatigue, muscle pain, joint pain, headache. Anyway, side effects were transient, started about 15 hours after vaccination, and resolved mostly within two days.
Specifically, the most common adverse event was pain at injection site, which was observed both after first and second dose administration more frequently in the vaccinated group rather than in the placebo group. Pain was mild and lasted up to three days. Less than 1% of the participants showed mild reactions at the injection site eight days after injection, but they resolved in about five days.
Systemic adverse events were reported both in the vaccine and placebo group, though slightly more frequently in the vaccine group, mainly after the second dose. Overall, severity of side effects in vaccine group increased after the second dose. Anyway, side effects lasted no more than three days. Overall, adverse events were more common in young adults (younger than 65) than in older participants (older than 65).
Efficacy. The vaccine showed a 94.1% efficacy in preventing the disease.
Specifically, 14 days after the first dose, 225 cases of covid-19 disease were registered in the placebo group and 11 (over 15.210 vaccinated participants) in the vaccinated group. Concerning efficacy in preventing severe Covid-19 disease, the 30 participants in the trial who had severe Covid-19 symptoms were in the placebo group, not in the vaccine group, demonstrating in this case a 100% efficacy in preventing severe covid-19 disease.
Vaccine efficacy was consistent among all age group analysed (meaning group 1 including people aged 18-65 years old and group 2 including people older than 65 years old).
Overall efficacy was comparable to the BioNTech/Pfizer vaccine, and was higher (at least in the 2-month follow-up analyzed) than efficacy (59%) recorded for seasonal influenza virus vaccine, made with attenuated virus. A two year follow up is planned. Pregnant women and children were excluded from this trial, requiring additional evaluation in future trials.
Higher storage temperature (2-8°C) of this vaccine compared to that required for BioNTech/Pfizer vaccine may be important considering that while big structures may have the possibility to easily store –and so distribute– vaccines that need lower storage temperature, smaller structures (such as family doctors) may more easily store and distribute this vaccine.
ChAdOx1 nCoV-19 vaccine (AZD1222, Oxford-AstraZeneca). The AZD1222 vaccine is a little different from the BioNTech/Pfizer- and Moderna/NIAID- developed vaccines, being constituted by a DNA vector (a DNA molecule) containing the gene coding for the SARS-CoV2 spike protein.
On January 9th The Lancet reported collective results of four trials conducted in UK, Brazil, South Africa. Differently from the BioNTech/Pfizer and Moderna/NIAID studies, the control group was injected with another vaccine, the A, C, W, Y meningococcal vaccine instead that with a placebo. Overall, the trial, conducted between April and November 2020, included 11.636 participants, 5.807 of them were injected with the AZD1222 vaccine, while 5.829 were injected with the meningococcus vaccine as control. The vaccination included two doses, however the time interval between doses was not the same in all the four trials, due to the time needed for manufacturing the vaccine. Not all participants received the same dose (some participants received the standard dose both at the first and second shot, while some others received half dose at the first shot and the standard dose at the second shot).
Safety. Across all four studies, the vaccine had a good safety profile. Only two subjects who received the AZD1222 vaccine had serious adverse events which were considered possibly related to vaccine administration: one case of myelitis (inflammation of the spinal cord) reported 14 days after second dose vaccine administration, and one person who had fever higher than 40°C, who anyway recovered rapidly and without requiring hospitalization.
Efficacy. Overall, the vaccine showed a 70% efficacy. Specifically, 30 Covid-19 cases among 5.807 vaccinated were recorded, compared to 101 cases over 5.807 participants in the control group. In detail, while efficacy was 62% among those who received two standard doses of the vaccine, 90% of efficacy was recorded among those who received a lower dose at the first shot and a standard dose at the second shot.
Interestingly, data previously published for the AZD1222 vaccine3 (on a smaller patient cohort) reported measurement of specific anti-SARS-CoV2 antibody (IgG against the viral spike protein) levels in the blood of vaccinated people, demonstrating the induced immune response, with the production of anti-SARS-CoV2 specific antibodies 28 days after the second dose. Similar antibody levels were measured regardless of the participant age (either 18-55, 56-69 or over 70 years old) and the dose of the vaccine administered. However, it has to be considered that such data were collected on very few patients; anyway, results highlighted the importance of the two-dose administration. Furthermore, the ability of the produced antibodies to neutralize the virus was comparable regardless of the dose administered or age group (one participant only, in the over 70 year old group, showed no neutralizing ability of the produced antibodies).
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In the past few days, AZD1222 (Oxford-AstraZeneca) vaccine efficacy in older adults has been highly debated. Doubts arouse from the low number of participants of this age group included in the trial. Participants included in the trial, for the three different vaccines approved, are the following: BioNTech/Pfizer vaccine: 10.889 in the 16-55 year group; 7.971 in the over 55 years old group. Moderna/NIAID: 8.886 in the 18-65 age group; 3.749 in the group of people older than 65 years. Oxford-AstraZeneca: 18-55 years: 5.089 participants; 56-69 years: 494 participants; over 70 years: 224 participants.
On January
30th vaccine administration has been approved by AIFA (Agenzia Italiana del Farmaco), although further data in this age group are expected from ongoing studies.
References.
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. L.R. Baden, H et al., The New England Journal of Medicine 2020.
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Merryn Voysey, Sue Ann Costa Clemens, Shabir A Madhi, Lily Y Weckx, Pedro M Folegatti et al., The Lancet 2021.
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1Spike proteins (proteins expressed on the viral surface and required to mediate infection) exist in two different forms: the so-called “pre-fusion conformation” before the virus enters and infects mammalian cells, which undergoes major rearrangements, adopting a different form, upon infection, when the virus fuses with the mammalian cell membrane. The RNA sequence of the vaccine has been slightly modified compared to the original sequence of the virus to prevent the rearrangements occurring during infection: the protein produced starting from the RNA molecule of the vaccine thus remains in the pre-fusion form.
2Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Corbett KS, Flynn B, Foulds KE, et al. N Engl J Med 2020.
3Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Maheshi N Ramasamy, Angela M Minassian, Katie J Ewer, Amy L Flaxman, Pedro M Folegatti, Daniel R Owens, Merryn Voysey, et al., The Lancet 2020.