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Highly pathogenic avian influenza H5N1 viruses are of global concern. This study shows that a low-dose H5N1 clade 2.3.4.4b Alum/CpG-adjuvanted vaccine elicits broad, durable antibody and T cell responses and protects female mice against lethal homologous and heterologous H5N1 challenges.

Understanding the dual role of neuraminidase and hemagglutinin antibodies in influenza transmission is crucial for enhancing vaccine efficacy. Here, the authors use household transmission studies and mathematical models and find that neuraminidase immunity reduces infectivity, suggesting vaccines targeting both glycoproteins could lower community transmission and offer broader protection.

Clade 2.3.4.4b highly pathogenic H5N1 is currently causing a panzootic and has the potential to become a pandemic. Here, Peña Alzua and colleagues develop specific monoclonal antibodies against this virus that could be used to prevent or treat human infections.

Structurally convergent antibodies targeting the conserved influenza HA anchor epitope have provided a template for next-generation vaccine development. The authors identified four anchor antibodies encoded by diverse germline genes with broad neutralizing activity against influenza H1N1 viruses.

Continued monitoring of population SARS-CoV-2 seroprevalence can reveal infection and vaccination patterns. Here, the authors report data from a prospective hospital-based sero-monitoring study in New York City from 2020–2023, including ~55,000 individuals.

In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.

Analysis of the immunogenicity of the Ad26.COV2.S vaccine against the B1.351 and P.1 SARS-CoV-2 variants of concern shows reduced neutralization antibody titres, but comparable T cell responses and antibody-dependent effector functions.

There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Schwaz, Austria, experienced SARS-CoV-2 outbreaks caused by variants of concern in early 2021 and conducted a mass vaccination campaign in response, with 70% of the adult population vaccinated after 5 days. Here, the authors show that this campaign resulted in reduced infections and hospitalisations.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

The authors report that an AS03-adjuvanted chimeric hemagglutinin-based influenza vaccine induces persistent stalk-specific serum antibody and bone marrow plasma cell responses in nonhuman primates, offering promise for broader and durable flu protection.

Sera from unvaccinated, vaccinated, and previously infected and vaccinated individuals show reduced neutralizing and spike protein-binding activity towards the Omicron (B.1.1.529) variant of SARS-CoV-2 compared to other variants.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Prior exposure to infectious agents can impact the vaccination induced immune response. Here the authors show prior SARS-CoV-2 infection results in more efficient induction of mucosal SARS-CoV-2 secretory IgA antibody following mRNA vaccination.

Antibodies that broadly inhibit influenza virus neuraminidase by binding to its active site could be therapeutic candidates, but circulating viruses have acquired a glycosylation site in that region. Here, the authors show that, while the S245N glycosylation site affects binding of tested monoclonal antibodies, protective activity in a mouse model is maintained.

Recent studies suggest that neutralizing antibodies could serve as a correlate of protection for vaccines against SARS-CoV-2 in humans.

Kaplonek et al. provide a prospective look at ChAdOx1 nCoV-19-vaccinated individuals who go on to experience breakthrough COVID infections. They report an antibody Fc profile characterized by higher FcgR2b and reduced Fcgr3b for individuals who are more susceptible to breakthrough infections.

Development of an enzyme-linked immunosorbent assay to detect antibodies to the SARS-CoV-2 spike protein in human sera and plasma.

In addition to SARS-CoV-2, other coronaviruses also infect human, but whether consecutive infections cross-modulate the induced immune response is still unclear. Here the authors show that SARS-CoV-2 infection boosts pre-existing responses to other coronaviruses, yet such back-boosting hampers the induction of specific antibodies against SARS-CoV-2.

Cryo-EM structures of the full-length Junin virus and Machupo virus spike glycoprotein complexes stabilized in the prefusion conformation. Analyses reveal features that regulate glycoprotein pH-dependent membrane fusion activity.

The public health concern caused by influenza B virus is often overlooked, yet represents a significant global burden. Here, the authors evaluate the cellular and humoral immune responses of multivalent vaccine candidates, based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA platform, and demonstrate protection of mice from challenge with a broad panel of influenza B viruses.

The recently identified Wuhan spiny eel influenza virus (WSEIV) sequence is more closely related to influenza B than A viruses. Here, the authors functionally characterize the putative surface glycoproteins of WSEIV and show that its NA-like protein has sialidase activity and its HA-like protein binds monosialic ganglioside 2.

Study of influenza virus transmission in humans provides evidence that hemagglutinin stalk-specific antibodies correlate with protection from infection.

Antigenic drift and reassortment alters the epitopes of influenza virus. Krammer and colleagues reveal the cross-reactivity of antibody responses to viral hemagglutinin and neuraminidase in humans and several animal models, but the most prominent responses reflect ‘original antigenic sin’ to viral exposure.

Seropositive samples of SARS-CoV-2 were detected as early as mid-February in patients at Mount Sinai Hospital in New York City, and antibody positivity increased during the first wave of the pandemic and remained stable afterwards.

Current influenza vaccines are effective but require reformulation each year and do not protect against pandemic influenza strains. Here, Krammer and Palese discuss the advances in the design and production of seasonal and pandemic influenza virus vaccines, including novel vaccine constructs and adjuvants. Advances in the design of universal influenza vaccines are also presented.

To overcome the limitations of seasonal influenza virus vaccines and enhance our pandemic preparedness, influenza virus vaccines that provide universal and long-lasting protection are needed.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

A multivalent vaccine that presents diverse influenza virus subtype H1 hemagglutinins on its surface induces broadly neutralizing antibodies in an animal model by displaying conserved epitopes at higher density than strain-specific epitopes.

Recent evidence of transmission of avian H5N1 viruses among mammals raises concerns about their pandemic potential. We need to increase our awareness and preparedness, and should also be thinking about safe farming practices to prevent the emergence of concerning pathogens in the future.

Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.

This study reports the identification of broadly protective antibodies targeting the influenza B neuraminidase away from its active site. One dose of antibody therapy was more protective in mice than multiple doses of the current standard of care.

Following the success of the COVID-19 vaccines, mRNA vaccines have now entered development for a wide range of infectious diseases. This Review discusses mRNA vaccine design considerations, delivery strategies and mechanisms of action, assessing mRNA vaccines currently in development for various viruses, bacteria and parasites. The challenges, limitations and opportunities facing next-generation mRNA vaccines are considered.

COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen associated with morbidity and mortality in the immunocompromised or immunonaive context. Here the authors show that HCMV exploits STING signalling and subverts the interferon response to support infection of monocyte derive dendritic cells.

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

A technique known as scSLAM-seq that combines single-cell RNA sequencing with metabolic RNA labelling and nucleoside conversion is used to study the onset of cytomegalovirus infection in single mouse fibroblasts.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

The human germinal centre response to influenza virus vaccination is fuelled by the continued recruitment of naive B cells as well as pre-existing memory B cells.