COVID-19 vaccines

Inserm – ANRS MIE

Giuseppe PANTALEO, MD, PhD – CHUV (Lausanne, Switzerland) -Yves LEVY, MD, PhD – AP-HP

The currently approved COVID-19 vaccines trigger immune responses to the Spike (S) protein of SARS-CoV-2 with the aim to elicit neutralizing antibodies. However, the long-term efficacy of the authorised mRNA vaccines has been impacted by the limited durability of the immune responses induced by these vaccines and by the continuous emergence of variants of concerns.

ANRS0711s SOLVE-01 trial will evaluate the safety and immunogenicity of experimental subunit proteins vaccines (CD40.RBDv and CD40.Pan.CoV) used as heterologous boost in volunteers previously vaccinated with authorized mRNA vaccines. The durability of the antibody responses induced by these experimental vaccines will be evaluated to that of currently deployed vaccines (Nuvaxovid^TM and Comirnaty®).

Phase I, open-label randomised multicentre experimental medicine trial including four different boost strategies (12 healthy participants included per group):

• Group 1: Boost with CD40.RBDv vaccine adjuvanted with Hiltonol®
• Group 2: Boost with Pan.CoV vaccine adjuvanted with Hiltonol®
• Group 3: Boost with Comirnaty® vaccine
• Group 4: Boost with Nuvaxovid™ vaccine

To determine the safety and reactogenicity of a booster injection between D0 and W4.

To determine the humoral immune response (neutralizing antibody titers, NeutAbs) induced by a booster vaccine at W4 and W48 (for durability).

Proportion of participants without any grade 3 or 4 solicited local/systemic or unsolicited AEs between D0 and W4 and considered to be related or possibly related to IMP administration.

Geometric mean titers of NeutAbs against the original strain D614G and the relevant circulating variants measured at W4 and W48.

Healthy adult volunteers having received at least two doses of COVID-19 mRNA vaccines in the past with the last dose received more than 6 months prior to IMP administration, age between 18 and 65 years

Volunteers meeting the eligibility criteria are randomly allocated in a 1:1:1:1 ratio at trial entry to start one of the four open-label SARS-COV-2 vaccine strategies.

48 healthy participants

2 sites in France (Créteil, Paris) and 1 site in Switzerland (Lausanne)

24 months

The ANRS0711s SOLVE-01 project has received funding from the European Union’s Horizon Europe Research and innovation program (Project number: 101137185).

Methodological aspects, trial coordination, monitoring, data management and statistical analysis