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Does vaccine efficacy depend on antibody levels?

In the fight against the COVID-19 pandemic it is important to have a varied arsenal of safe and effective vaccines. Since global demand is high, prices must remain low enough to ensure equitable worldwide distribution. To complicate matters, we do not have data on vaccine efficacy for certain sectors of the population (pregnant women, children, immunocompromised individuals or people with auto-immune diseases) and more transmissible variants regularly emerge. In vaccine research, correlates of protection (immunological markers that predict vaccine efficacy) are highly sought after. Antibodies have often played this role against several viral illnesses.

It was a multidisciplinary American team ((Moderna, Cambridge; Fred Hutchinson Research Centre, Seattle; the American Government; NIH, Bethesda; the American Consortium of Universities) which estimated the efficacy of the Moderna vaccine at 94% during phase 3 COVE tests, thereby enabling its distribution. At the same time, they tried to establish whether levels of blood antibodies could be used as correlates of protection. They assessed blood levels of anti-spike, anti-RBD and neutralizing antibodies, just after the 2nd injection and then 4 weeks later (on days 29 and 57). By day 57, all participants had developed anti-spike and anti-RBD antibodies, with 82% having satisfactory levels, enough to neutralise 50% of the virus (expressed by an ID50). Levels of anti-spike or anti-RBD antibodies are therefore linked to levels of neutralising antibodies.

The researchers then measured the risk of developing COVID-19 in a 4 month period (more specifically, by natural infection with the original virus strain). The statistics showed that the more the level of neutralising or anti-spike antibodies increases, the less patients are at risk of falling ill. So, the higher the level of antibodies, the greater vaccine efficacy. For the 10% of individuals who have developed the most antibodies, there is effectively 10 times less risk. The action of neutralising antibodies accounts for 2/3 of vaccine efficacy.  

This work clearly establishes that the level of neutralising antibodies triggered by a vaccine constitutes an excellent immunological marker to evaluate its efficacy and enable its validation. Protection does not fall to zero below a certain baseline antibody level, but a continuous increase in antibody levels progressively decreases the risk of COVID-19.

However, the study has certain limits. Do its conclusions hold in the case of  variants? Is the level of antibodies pertinent no matter what the levels of virus load in patients? The study also did not consider the role of cellular immunity. However, selective short-term trials (on children for example, or with modified doses, or with the 3rd vaccine dose) would allow comparison of levels of induced antibodies with the figures produced by this study. It is perhaps less valid for other studies necessitating more caution and using other criteria, such as the evaluation of long-term protection, the testing of a new vaccine produced on the same platform, or modification of the spike in the same vaccine. The participants in this study will be monitored for 2 years, so as to evaluate long-term vaccinal protection, the decrease in antibody levels, and protection against new variants.

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