Vaccines

Dengue is one of the most rapidly spreading arboviral diseases worldwide, and the development of effective vaccines has long been constrained by antibody-dependent enhancement (ADE) and the difficulty of inducing protective immunity against multiple viral serotypes. Although several live-attenuated dengue vaccines have received regulatory approval in different jurisdictions, including Dengvaxia (CYD-TDV), Qdenga (TAK-003), and, more recently, Butantan-DV in Brazil, important challenges remain regarding vaccine safety in relation to pre-vaccination dengue serostatus, balanced cross-serotype protection, and the durability of vaccine-induced immunity. This review focuses on the immunopathogenic mechanisms of dengue virus infection, with particular emphasis on how ADE and immune bias impose critical constraints on vaccine design. We systematically summarize the technological platforms, immunological rationale, and major limitations of licensed and investigational dengue vaccines. Building on this analysis, the potential advantages and remaining challenges of emerging vaccine technologies, particularly mRNA vaccines, in precise antigen design, multivalent immune regulation, and safety optimization are further discussed. This review aims to provide a theoretical basis and strategic reference for the development of next-generation dengue vaccines with improved safety and efficacy.

Background/Objectives: Local manufacturing of Measles-Rubella (MR) vaccines is part of a multifaceted approach to improve vaccine accessibility in Africa, yet process development and technology transfer challenges remain for large-scale production of viral bulks and lyophilized drug product. This case study describes lab-scale formulation development of a multidose, lyophilized MR vaccine candidate, leveraging the availability of concentrated bulks of Measles (MeV) and Rubella (RuV) produced in MRC-5 cells by a new bulk manufacturing process. Methods: Formulation studies utilized both high-throughput RT-qPCR viral infectivity assays and standard lyophilization measurements. The off-patent, publicly available formulation composition of a single-dose, lyophilized trivalent MMR vaccine was evaluated as a starting point to develop a multidose, bivalent lyophilized MR vaccine candidate. To identify optimized conditions, various formulation (e.g., human serum albumin, viral bulk volume), drug product (e.g., vial size, fill volume), and lyophilization (e.g., freezing rate, primary/secondary drying cycle) parameters were evaluated to lower costs and assess MR stability during lyophilization, storage, and reconstitution. Results: Real-time and accelerated stability studies were conducted with four variations of the top candidate MR formulation, filled into primary packaging selected for technology transfer and lyophilized in both lab- and pilot- scale freeze-dryers. An optimized five-dose MR vaccine formulation with 5% (v/v) bulk and 95% (v/v) stabilizer solution, filled at 2X and reconstituted to 1X concentrations, demonstrated promising stability profiles and cost reduction potential. Stability profiles at 2–8 °C were used to estimate the MR release doses needed to ensure the required expiry doses at end of shelf-life. Conclusions: Results are discussed, along with recommendations for future work, in the context of the analytical, formulation, and lyophilization challenges encountered during lab-scale development of a candidate multidose, lyophilized MR vaccine dosage form targeted for technology transfer and large-scale local production in Africa.

Background: Nowadays, poliomyelitis caused by wild polioviruses (PVs) has been virtually eradicated. However, since the removal of the type 2 component from the oral polio vaccine (OPV), immunity to PV2 has declined despite expansion of the use of the inactivated polio vaccine (IPV). Unfortunately, sources of neurovirulent PV2 remain in the world in the form of vaccine-derived poliovirus type 2 (VDPV2) cases and outbreaks and immunodeficient iVDPV2 excretors. Methods: Neutralizing antibodies (nABs) in sera from children with different numbers of IPV/OPV doses were evaluated against VDPV2 strains. Results: A genetic analysis of four VDPV2 strains with varying genetic divergence from Sabin 2 (4.32–17.39%) revealed a number of mutations in antigenic sites. We observed that 6.5–51.8% of undervaccinated (1–2IPV) children did not have nABs against at least one studied VDPV2. Fully vaccinated children showed almost 100% neutralization, although 3.1% vaccinated with 3IPV did not have nABs against three VDPVs; 4.5% vaccinated with 3IPV + 1bOPV and 2.5% vaccinated with 5tOPV did not have nABs against the most divergent iVDPV2 strain. Conclusions: Therefore, some fully vaccinated children may not have detectable levels of protective nABs against VDPV2.