Refining the DC-targeting vaccination for preventing emerging infectious diseases

Abstract

The development of safe, long-term, effective vaccines is still a challenge for many infectious diseases. Thus, the search of new vaccine strategies and production platforms that allow rapidly and effectively responding against emerging or reemerging pathogens has become a priority in the last years. Targeting the antigens directly to dendritic cells (DCs) has emerged as a new approach to enhance the immune response after vaccination. This strategy is based on the fusion of the antigens of choice to monoclonal antibodies directed against specific DC surface receptors such as CD40. Since time is essential, in silico approaches are of high interest to select the most immunogenic and conserved epitopes to improve the T- and B-cells responses. The purpose of this review is to present the advances in DC vaccination, with special focus on DC targeting vaccines and epitope mapping strategies and provide a new framework for improving vaccine responses against infectious diseases.

Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design

“…Indeed, this strategy has already been applied successfully to subunit vaccines ( 32 – 34 ). Altogether, DC targeting could potentially not only improve mRNA vaccine efficacy, but also expand the range of pathogens for which they do effectively work, including those that have developed mechanisms to bypass the immune system, which are some of the most challenging to address ( 35 ).…”

A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease

“…From a clinical perspective, the CD40.NiV vaccine was administered to AGMs with the clinical-grade poly-ICLC adjuvant, as previously done for HIV DC-targeting vaccines in preclinical models 15 , 18 and in healthy volunteers enrolled in the first human phase 1 trials to test the CD40.HIVRI.Env vaccine (ClinicalTrials.gov: NCT04842682 ), demonstrating the safety and immunogenicity of the vaccine. 38 However, the capacity to induce protective immunity without requiring an adjuvant 14 would accelerate the development of a protein-based vaccine with improved tolerability over adjuvanted vaccines, making it suitable for specifically vulnerable individuals and children. Indeed, licensed subunit vaccines have demonstrated tolerability and safety in diverse population groups, including pregnant women and children.…”

“… 39 Further studies in non-human primates should be conducted to determine the minimal amount of CD40.NiV required to induce protective responses and/or the need for an adjuvant. 14 …”

“…Among the various DC receptors tested, including lectins and scavenger receptors, we have reported the superiority of vaccines that target diverse viral antigens to CD40-expressing antigen-presenting cells (APCs) in evoking strong antigen-specific T and B cell responses. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 Drawing from this knowledge, we developed a vaccine that targets selected epitopes from the G, F, and nucleocapsid (N) proteins from NiV-B. Here, we report the immunogenicity and protective efficacy of an anti-CD40 multi-epitope Nipah prophylactic vaccine in African green monkeys (AGMs) exposed to an experimental challenge with the NiV-B virus.…”

SARS-CoV-2: Immunity, Challenges with Current Vaccines, and a Novel Perspective on Mucosal Vaccines

“…APCs have long been a target for vaccine development due to their central role in antigen processing and presentation [193][194][195][196][197][198][199][200][201][202]. FcγRI is an activating receptor with an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain and is expressed exclusively on macrophages and DCs, which makes it uniquely suitable for APC targeting [203][204][205].…”