By applying mRNA technology and structural engineering, researchers have fashioned an advanced antibody therapy that can neutralize SARS-CoV-2 while constraining the virus’ ability to escape recognition. The therapy protected mice against infections with an immune-evasive Omicron variant, and provides a structural template for antiviral antibodies that can keep up with their constantly evolving viral targets. Although the COVID-19 pandemic is over, SARS-CoV-2 remains a threat to public health, and is especially dangerous for people with compromised immune systems who can’t fully benefit from vaccines. Antibody therapies are critical for these high-risk groups, as they can bind to and neutralize the virus without the need for vaccine-induced immunity. However, like other viruses, SARS-CoV-2 is constantly evolving – and variants quickly appeared that could evade the first generation of antibody therapies. This escape has also undermined the deployment of next-generation antibodies, so new approaches are needed. Here, Anna Wec and colleagues used high-throughput screening and isolated several antibodies from llamas that could neutralize the XBB.1.5 and JN.1 variants of SARS-CoV-2. The researchers engineered these lead candidates into more potent bispecific antibodies, which can target multiple sites on the same protein. Furthermore, they introduced structural modifications that allow multiple antibodies to be delivered in tandem via mRNA. This mRNA strategy maximizes the antibodies’ ability to target SARS-CoV-2 as it evolves, and could potentially lower the high costs and manufacturing complexity that have held back previous bispecific antibody therapies. The platform neutralized a broad range of historical and current SARS-CoV-2 variants in serum and protected mice against infections with XBB1.5. “This platform may have applications in other therapeutic areas in which broad antigen coverage, resistance to escape, or simultaneous engagement of multiple disease-associated targets is desirable,” Wec et al. write.

Researchers in India have used an AI-based molecule generation platform to design a novel compound that computationally blocks one of the most conserved and functionally essential enzymes of SARS-CoV-2 — the main protease — with drug-like properties, no predicted toxicity, and a binding profile that compares favourably with clinically studied inhibitors, making it a candidate worth pursuing for further laboratory validation.

A study of more than 700 people has shown that those with long Covid have distinct differences in the mix of bacteria that live in their mouths and lungs, according to a study published in the European Respiratory Journal. Researchers say their findings may shed light on why some people develop long Covid and they could point to new ways to treat the condition.

A person’s microbiome may help determine whether they develop a fever after receiving a vaccination, according to a new study. The findings suggest that the microbiome and potentially diet could one day be targeted to reduce vaccine-related inflammation without compromising the immune protection vaccines provide. Vaccines are a crucial tool for ensuring public health, but people vary widely in their immune responses and side effects. Fever and flu-like symptoms are among the most common adverse reactions to vaccines, particularly mRNA- and lipid nanoparticle-based vaccines. These reactions can discourage future vaccination and contribute to vaccine hesitancy and mistrust. However, not all those who receive a vaccination develop a fever and those who do tend to get a fever across repeated doses, suggesting the importance of individual risk factors for fever. The reasons for this variation are not well understood.

In this study, Kelsey Huus and colleagues speculated that the gut microbiome, which is known to influence immune activity, may play a role in driving these reactions. To test this hypothesis, Huus et al. profiled the fecal microbiomes, body temperature, and blood-based immune markers of 171 healthy adults before and after receiving the mRNA vaccination for SARS-CoV-2. The findings showed that certain gut bacteria, especially Lachnospiraceae, produce flagellin, which can activate inflammatory immune pathways and intensify vaccine-related reactions. Those who had greater pre-vaccination intestinal inflammation or higher levels of flagellin expression in the gut tended to develop vaccine-induced fever. What’s more, the authors found that industrialized diets may promote this inflammatory activity. Vegetarian diets tended to correlate with microbiome features that contributed to less fever, while lower consumption of whole plant foods and diets characterized by greater fat or processed-food intake were associated with the inflammatory, fever-associated microbiome. Dietary manipulation altered both microbiome compositions and their associated vaccine responses. Importantly, Huus et al. show that flagellin, inflammation, and diet do not affect antibody responses to vaccines, suggesting that the microbiome-driven inflammation increased vaccine side effects without necessarily affecting immunity. “Diet, microbial ecology, and the metabolic state are not immutable, and people might one day prepare for vaccination as deliberately as the vaccine itself is formulated,” writes Bali Pulendran in a related Perspective.

Major societal events such as the Brexit referendum and Covid-19 lockdowns have contributed to the UK’s lasting deterioration in mental health, finds a study led by University College London (UCL) researchers.