Vaccines

Annual influenza vaccination remains critical for mitigating severe illness and reducing healthcare strain, particularly among high-risk populations. Despite advancements in vaccine platforms, the comparative efficacy of novel vaccines—such as high-dose (HD-IIV), recombinant (rIV), cell-based (cIV), and adjuvanted (aIV) influenza vaccines—versus standard-dose non-adjuvanted (SD-IIV) vaccines remains a public health concern. Traditional Relative Vaccine Efficacy (rVE) metrics, though robust, may overestimate population-level benefits. This short communication explores alternative comparative efficacy measures: risk difference (ΔRD) and number needed to vaccinate (ΔNNV). Analysis of data derived from randomized controlled trials (RCTs), or robust pragmatic trials, shows that while rVE values for newer vaccines often indicate superior efficacy, ΔRD and ΔNNV highlight the limits in incremental protection at the population level, with ΔRD generally below 10 cases per 1000 vaccinated. These findings underline the sustained relevance of SD-IIV in immunization programs and emphasize the need for broader vaccine coverage to highlight the benefits of vaccination and enhance population health outcomes.

The development of cancer immunotherapies has transformed cancer treatment paradigms, yet durable and tumour-specific responses remain elusive for many patients. Neoantigens, immunogenic peptides arising from tumour-specific genomic alterations, have emerged as promising cancer vaccine targets. Early-phase clinical trials using different vaccine platforms, including mRNA, peptide, DNA, and viral vector-based personalised cancer vaccines, have demonstrated the feasibility of targeting neoantigens, with early signals of prolonged survival in some patients. Most current vaccine strategies focus on canonical neoantigens, typically derived from exonic single-nucleotide variants (SNVs) and small insertions/deletions (INDELs), yet this represents only a fraction of the potential neoantigen repertoire. Evidence now shows that non-canonical neoantigens, arising mostly from alternative splicing, intron retention, translation of non-coding RNAs, gene fusions, and retroelement activation, broaden the antigenic landscape, with the potential for increasing tumour specificity and immunogenicity. In this review, we explore the biology of non-canonical neoantigens, the technological advances that now enable their systematic detection, and their potential to inform next-generation personalised cancer vaccines.

Background/Objectives: While new vaccines are in development; one strategy to increase influenza vaccine coverage is to repurpose current influenza vaccines for intranasal delivery. Methods: To address this goal; mice were vaccinated intranasally with either a split inactivated virus vaccine (Fluzone) or a recombinant HA vaccine (Flublok) at one of two doses (1 μg high dose or 0.1 μg low dose). Both vaccines were adjuvanted with either a STING agonist; c-di-AMP (CDA); or a combination of a synthetic toll-like receptor (TLR) 4 and TLR7/8 agonist (TRAC478). Results: Mice vaccinated with either vaccine plus adjuvant had higher hemagglutination-inhibition titers than mice administered unadjuvanted vaccines. Mice vaccinated with either vaccine plus CDA had on average higher numbers of H3 and influenza B hemagglutinin (HA)-specific antibody-secreting cells (ASCs); whereas mice vaccinated with vaccine plus TRAC478 had on average higher number of H1 HA-specific ASCs. All vaccinated mice challenged with the H1N1 influenza virus were protected against both morbidity and mortality with no detectable virus in their lungs. Mice challenged with the H3N2 influenza virus all lost weight over the first 5 days of infection. Adding TRAC478 with either a high or low dose vaccine resulted in 80–100% survival following challenge. Almost all mice vaccinated with Flublok plus CDA died from H3N2 influenza virus challenged with ~2 logs higher viral lung titers than mice administered Flublok only or Flublok plus TRAC478. Conclusions: Overall; Fluzone and Flublok can effectively be used for intranasal vaccination.