Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Abstract

The enormous sequence diversity between human immunodeficiency virus type 1 (HIV-1) strains poses a major roadblock for generating a broadly protective vaccine. Many experimental HIV-1 vaccine efforts are therefore aimed at eliciting broadly neutralizing antibodies (bNAbs) that are capable of neutralizing the majority of circulating HIV-1 strains. The envelope glycoprotein (Env) trimer on the viral membrane is the sole target of bNAbs and the key component of vaccination approaches aimed at eliciting bNAbs. Multimeric presentation of Env on nanoparticles often plays a critical role in these strategies. Here, we will discuss the different aspects of nanoparticles in Env vaccination, including recent insights in immunological processes underlying their perceived advantages, the different nanoparticle platforms and the various immunogenicity studies that employed nanoparticles to improve (neutralizing) antibody responses against Env.

Keywords: HIV-1 Env; liposomes; self-assembling protein nanoparticles; virus-like particles.

Figure 1

A meta-analysis comparing neutralizing responses induced by native-like Env trimers on nanoparticles or as soluble immunogens. The autologous neutralization data from rabbits and non-human primates were taken from the following studies: for BG505: [60,71,72,81]; for JRFL: [56]; for 16055 [59]; for ConM [74,81]. To avoid bias caused by differences in immunogenicity between these Envs, we first determined the geometric mean for each study at time of peak neutralization titer (i.e., two weeks after the last immunization). Subsequently, the relative neutralization titers of the individual sera were calculated using the geometric mean. When no neutralization was detected (i.e., 50% neutralization titer of <20), the value of this animal serum was set to 0.1. (A) NAb titers from animals immunized with BG505, JRFL, 16055 and ConM NPs or soluble Env. (B) NAb titers from animals only immunized with BG505 NPs or soluble Env (left); NAb titers from animals immunized with JRFL, 16055 and ConM NPs or soluble Env (right). Fold differences were calculated by comparing geometric means (denoted by horizontal red lines) between the two data sets. A Mann–Whitney U test was used to determine significance.