New vector and vaccine platforms: mRNA, DNA, viral vectors.

PURPOSE OF REVIEW: The purpose of this review is to share the excitement of new developments in the field of vaccine vector modalities against infectious diseases. The focus is on HIV-1/AIDS with reference to the most successful as well as currently tested COVID-19 vaccines, and human trials, which best inform iterative vaccine improvements. RECENT FINDINGS: Several genetic subunit vaccines against SARS-CoV-2 demonstrated protection against severe disease, obtained Emergency Use Authorization and scaled their production to billions of doses. Many more are in efficacy evaluation. In contrast, development of HIV-1 vaccines has been extremely difficult. Perseverance of scientists is deepening our understanding of what constitutes immunity against HIV-1 infection and how to achieve protective levels of relevant responses by active immunization, passive administration or a combination of both. Novel platforms led by RNA play a pivotal role. However, a difficult virus may require a complex approach. Proof of concept for HIV-1 prevention and cure might be at reach, and when it arrives, it will be a great and needed encouragement to the field. SUMMARY: Despite the enormous success of drug treatment, vaccines remain the best solution and likely a necessary component of any package that truly ends the AIDS epidemic.

USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.