Excellent preliminary results from Moderna’s phase 2/3 trial for an updated booster vaccine are coming from the United States. The new mRNA1273-214 vaccine is a bivalent version of the old Moderna vaccine coupled with the new booster built on the Omicron variant.
We have learned that viral circulation results in the accumulation of mutations and these mutations sometimes give rise to new variants. The new variants in addition to having new characteristics such as greater contagiousness or virulence diversity are characterized by the ability to escape from our immune system.
We know that the immune system is ‘trained’ by the vaccine which shows a part of the virus, the Spike protein, as a reference for the whole virus. Once the whole virus enters our body, the immune system is ready for attack as it has been trained in the past by the vaccine‘s Spike protein.
The problem arises when the virus accumulates many mutations on the Spike protein that should be used by the immune system as a ‘mugshot’ to recognize it.
The Omicron variant, for example, has accumulated so many mutations on the Spike protein, that the neutralizing antibodies generated by the old vaccine are not sufficient to neutralize it, resulting in infections of vaccinated or cured subjects.
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Fortunately, we know that neutralizing antibodies are not the only element of our immune system to be able to prevent infection and disease. In fact, despite the very high immunoevasiveness of the Omicron variant, the immune system of most of the infected was able to keep the virus at bay avoiding the severe form of the disease.
The continuous immunoevasive mutations underline the need for an updated vaccine or a pan-coronavirus vaccine, that is, a vaccine built in such a way as to induce an immune response even against variants of the future.
Preliminary results show that the bivalent vaccine is able to trigger a much higher antibody production than the classic vaccine. The antibodies produced are able to ‘neutralize’ the Omicron variant in vitro and remain in the plasma after months.
The data presented at the moment are in vitro that is obtained with experiments in the laboratory and before knowing if this version of the vaccine will work we must wait for the in vivo data, ie on the population. If the mRNA1273-214 vaccine were able to obtain excellent protection results even in the population, the approval by the FDA or other regulatory bodies would not be immediate, in fact for today a regulatory body to approve a new vaccine against Covid19 must be demonstrated in a manner robust and incontrovertible that the new vaccine is more effective than the approved ones.
Why a bivalent vaccine?
The bivalent Moderna vaccine seems to work better than the single versions that compose it, why? Our immune system probably needs the fullest spectrum of mutations to ‘get an idea’ of the virus and to be able to fight it in case of infection.
Moderna’s bivalent vaccine contains all the mutations on the Spike protein that characterize the Omicron variant and this allows the vaccine to stimulate the production of neutralizing antibodies against the different Omicron sub-variants (BA.1 / 2/4/5).
This ability of our immune system is called cross-reaction, in practice some mutations are sufficient to stimulate a broader immune response that covers more mutations. For example, the immunity induced by the Omicron sub-variant BA.1 seems to confer protection also against the other BA4 / 5 sub-variants.
The complete data of this trial are expected in early autumn when an updated booster dose could be essential, in fact we know that in winter the cases will rise again and by then many people will have lost many antibodies induced by the previous vaccination due to the phenomenon of waning anticorpale.
TAKE HOME MESSAGE:
- Moderna has developed a bivalent vaccine to be used as a booster
- The vaccine contains an original and a specific version against Omicron
- The combination of these two vaccines is very effective in vitro against omicron and its sub-variants
- Real security data should arrive in the fall
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