Reacción a "A phase 3 clinical trial has tested a new RNA vaccine against influenza"

This study compares an RNA vaccine against influenza A (A/H3N2), A (A/H1N1), B (B/Yamagata), and B (B/Victoria) strains with a commercially available vaccine containing inactivated viruses of these four influenza strains.

The study demonstrates that the RNA vaccine does not induce a weaker immune response than the conventional vaccine and provides superior short-term protection. However, it induces greater reactogenicity, with effects such as fatigue, fever, headache, and injection site pain being more pronounced than those observed with the control vaccine.

A large number of participants were included in this phase III trial, but the efficacy results for both vaccines in preventing infection were modest, with a relative efficacy of 35.8% at seven days post-vaccination and similar efficacy at 14 days post-vaccination. Figure 1 shows a relative vaccine efficacy of 34.5%, although higher for the RNA vaccine than for the inactivated virus vaccine. In the analysis at the end of the flu season, the relative efficacy of the vaccine was 28.7%, which is a very modest efficacy.

Studies of cellular response were carried out with analysis of interferon-gamma production by both CD4+ and CD8+ lymphocytes. A greater response was observed than that achieved by the inactivated viruses of the commercial vaccine, especially for T helper lymphocytes, while for CD8+ lymphocytes, two A strains did not induce a good CD8+ cellular response.

Detailed analysis:

1. The study of the immune response is short-term, with a period of 130 days to analyze cases of infection, but the study of the immune response and the neutralizing capacity of hemagglutinin was performed soon after inoculation of the vaccine.
2. Of the four strains studied (two of A and two of B), Yamagata has not been circulating for several years, and, in fact, the WHO recommended in September 2023 not including it in vaccines, recommending that trivalent vaccines be produced with only 3 strains (2 of A and one of B).
3. It is interesting to note that the response obtained against strain B (B/Victoria) in relation to hemagglutinin neutralization capacity and seroconversion is very low with the mRNA vaccine, compared to the commercial control vaccine.
4. Volunteers aged 18-64 years, with a more robust immune system than those over 65, who are the target population for this type of vaccine, have been studied. The limited protection induced by this vaccine indicates that either the sequences included in the vaccine did not correspond to the strains that caused the infection, or that the vaccine does not elicit a good immune response.
5. This new mRNA vaccine has been compared to another commercial vaccine, not a placebo, which leads to studying relative rather than absolute efficacy, as the authors themselves indicate as a limitation of their study. However, it is very interesting to have a comparative study of two vaccines.
6. This type of vaccine can be produced in less time than traditional vaccines, but it should focus on the most vulnerable target population. A relative efficacy of 28.7% has considerable room for improvement.
7. The responses in children, another population highly vulnerable to influenza, have not been studied either.
8. The greater reactogenicity of a vaccine that would foreseeably need to be administered annually, depending on the changing circulating strains, could be a problem for public acceptance.