Next-generation vaccines for infectious diseases

The initial immune response following mRNA vaccine injection is not entirely clear. Here, the authors comprehensively profile injection site responses using single-cell transcriptomics in a mouse model showing activation of major axes of innate immune responses upon and the role of IFN-β to promote cellular immunity.

As part of a randomized controlled trial in Viet Nam, this study finds that pneumococcal-specific memory B cells (B_mem) are higher following a 1 + 1 compared to a 0 + 1 pneumococcal conjugate vaccine (PCV) schedule and higher for PCV13 compared to PCV10. B_mem did not wane as rapidly as IgG by 24 months of age.

Modified nucleosides are often used in mRNA vaccines and can affect protein expression and immunogenicity. Here, the authors compare M segment based Andes virus mRNA vaccines, either with regular uridine or N1-methylpseudouridine, and characterize immune response and protection in rodents.

COVID-19 vaccines have been associated with rare cardiovascular and thrombotic complications. Here, the authors use population-based longitudinal electronic health record data from ~46 million adults in England to quantify these outcomes following different vaccine doses and schedules.

In this work, the authors develop a platform called AGILE or AI Guided Ionizable Lipid Engineering, which streamlines ionizable lipid development. Using AGILE, they rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery.

The authors report an efficacious vaccine for human metapneumovirus based on a prefusion-stabilized fusion protein trimer that does not require a trimerization domain, designed using an AI convolutional classifier trained to predict optimized complex polar interactions.

Here the authors describe an intranasal vaccine that protects against multiple strains of SARS-CoV-2 and SARS-CoV while preventing transmission to vaccine naïve hamsters. Immunized monkeys elicit IgG and nasal IgA responses cross-reactive to several coronaviruses.

Here, the authors report results from a randomized, placebo-controlled phase 3 trial of the tetravalent SARS-CoV-2 protein vaccine SCTV01E, demonstrating a favorable efficacy profile during a time when predominant viral variants were changing from BA.5 and BF.7 to XBB.

Influenza genetic diversity is a key challenge in the design of a universal influenza vaccine that protects against different strains of influenza virus. Here, Malouli and colleagues demonstrate use of a cytomegalovirus-based T cell vaccine that induces immunity and can protect macaques from lethal avian influenza challenge with heterologous strains of influenza and suggest protection is linked to the generation of lung-resident influenza-specific CD4⁺ T cells.

Here the authors show that sequential immunization utilizing mRNA lipid nanoparticle (LNP) and protein-based nanoparticle vaccines can synergize to enhance influenza vaccine potency and breadth. Their mRNA LNP prime and intranasal protein nanoparticle boost strategy demonstrates optimal cross-protection against variant influenza strains.

In this study, the authors show that nanovaccines co-delivering EBV antigens and molecular adjuvants generate high levels of neutralizing antibodies targeting vulnerable EBV sites of gHgL, gB and gp42. Antibodies elicited by cocktail nanovaccine immunization provide durable protection against EBV-associated lymphoma.

BCG revaccination of adolescents has been shown to provide some protection against sustained infection with Mycobacterium tuberculosis. Here, using intracellular cytokine staining and CITE-Seq, the authors identify several effector memory CD4⁺ T cell populations in adolescents revaccinated with BCG that can aid the search for correlates of protection.

COVID-19 vaccines reduce the risk of severe disease in young people, but the absolute risk is low, and side effects have been reported. Here, the authors use data on 5–17 year olds in England to assess the overall risk-benefit profile of the vaccines.

Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.

Here the authors describe a stabilization technology that engineers crosslinks between tyrosine sidechains into a natively folded vaccine immunogen and show that immunogenicity is improved in small animal models by locking the most potently neutralizing epitopes.

Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.

Here the authors develop a mucosal SARS-CoV-2 vaccine and show immunogenicity and protection in mice as well as reduced virus transmission in hamsters. This protein vaccine consists of a stabilized spike protein fused to monomeric IgG Fc, supporting its transport across epithelial barriers by binding to the neonatal Fc receptor.

Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.

Here the authors use structure-based design to engineer a single component immunogen that mimics the malaria parasite AMA1-RON2 complex required for invasion of host cells, and show that it elicits a potent strain-transcending antibody response in rats.

Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.