The HIV-1 envelope glycoprotein (Env) is the only target of antigen design for antibody-based vaccines. Inducing broadly neutralizing antibodies against the Env protein would be a major step towards having a prophylactic vaccine capable of curbing the HIV pandemic. The development of stabilized, native-like trimeric Env immunogens, such as SOSIP proteins, has advanced the HIV-1 vaccine field. ConM SOSIP.v7 (ConM) is a native-like HIV-1 Env trimer, based on an artificial consensus sequence of all HIV-1 isolates in group M, responsible for the pandemic. When used to immunize non-human primates, ConM induces strong autologous neutralizing antibody responses. We aim to evaluate the safety of ConM in humans, as well as explore its immunogenic properties and provide proof-of-concept of the utility of native-like Env trimers as components of an HIV-1 vaccine regimen.
The ACTHIVE-001 study is a single center, phase 1 clinical trial at the Amsterdam UMC, the Netherlands (NCT03961438). 24 healthy participants are vaccinated with ConM at months 0, 2 and 6. Participants are randomized to receive either a consistent dose of vaccine, or a reduced booster dose at month 6, aimed to increase antibody responses and levels of somatic hypermutation. Safety information is solicited throughout a period of 18 months. Serological assays are performed, as well as lymph node fine needle aspirates (FNA) in order to investigate Env-specific germinal center (GC) responses. FNA samples are analyzed by nine colour flow-cytometry analysis.
At present, 24 participants received an accumulated total of 51 vaccine administrations (current median follow-up 9 months), while 13 participants are not yet fully vaccinated. No Serious Adverse Events or Suspected Unexpected Serious Adverse Reactions were observed. The majority of Adverse Events were mild to moderate and self-limiting in nature. 27 lymph node FNA’s were performed, with 20 yielding viable lymph node cells. In 11 (55 %) out of these procedures, ConM-specific B cells could be detected following one or two vaccinations. Strikingly, in some cases, > 90 % of ConM-specific B cells were GC B cells (Figure 1). Enrichment of ConM-specific B cells towards immunoglobulin G (IgG), compared to total B cells confirmed an isotype switch. Serological assays will be performed and correlated with FNA findings.
The ConM vaccine is safe when administered to humans and induces vaccine-specific germinal center reactions.