Inmaculada Casas
Head of the Respiratory Virus and Influenza Research Group of the Carlos III Health Institute
This study shows the results of a first-in-human Phase 1 clinical trial that has demonstrated that in healthy adults the new H1ssF vaccine is safe, well tolerated and immunogenic even without adjuvant. The vaccine generates broad-spectrum antibodies targeting the stem part of the viral hemagglutinin (HA), which serves the influenza A HA subtypes belonging to group 1 and is very poorly reactogenic.
The H1ssF vaccine consists of the elimination of the HA head where the antigenic sites are located and is therefore immunodominant.
The study is very complete and of very good quality.
H1ssF vaccine increased group 1 influenza binding antibodies in all age groups. In general, currently licensed influenza vaccines are less effective in older adults, but the authors show that the H1ssF vaccine does not differ in antibody responses as a function of age, so its use would be advantageous in those over 60 years of age.
Although an H1 antigen from the pre-2009 stem was used, the authors find adequate responses to stems diverging more than 20% in sequence from H1, including H5 and H2. The application for avian influenza prevention could be immediate.
In terms of limitations, the heterogeneity of pre-existing influenza immunity is an important confounding factor for the investigation of the immune response induced by new vaccines to be studied. In addition, according to the trial authors, the covid-19 pandemic slowed the progress of the trial and caused 23% of the participants to be lost.
By measuring antibody production against the stem, it can be proven to be immunogenic, i.e., antibodies are produced against the selected antigen. However, the vaccine effectiveness would be measured over the seasons with street viruses being replaced. With this assay, in my opinion, it would not be possible to speak of "global" vaccine effectiveness, because this would measure the protection of a vaccinated population against the viruses of the season, testing different seasons. It is noteworthy that the antibodies have been produced specifically against the antigen that they have constructed and that theoretically serves for several influenza subtypes (group 1).
Future studies will need to determine the optimal stem antigens for a safe, broad-spectrum influenza vaccine.