SARS-CoV-2 antibodies persist: As the number of daily COVID-19 cases continues to mount worldwide, the nature of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. Wajnberg et al. used a cohort of more than 30,000 infected individuals with mild to moderate COVID-19 symptoms to determine the robustness and longevity of the anti–SARS-CoV-2 antibody response. They found that neutralizing antibody titers against the SARS-CoV-2 spike protein persisted for at least 5 months after infection. Although continued monitoring of this cohort will be needed to confirm the longevity and potency of this response, these preliminary results suggest that the chance of reinfection may be lower than is currently feared. Science , this issue p. 1227

Alternative influenza target: There is a pressing need for a broadly protective influenza vaccine that can neutralize this constantly varying, deadly virus. Stadlbauer et al. turned their attention away from the current vaccine target—the mutable hemagglutinin—and investigated an alternative, less variable virus-coat glycoprotein: neuraminidase. The authors extracted monoclonal antibodies (mAbs) from a human donor naturally infected with the H3N2 virus subtype. In mice, the mAbs were broadly protective against influenza virus A groups 1 and 2 (human, avian, and swine origin) and some influenza B viruses. These mAbs were also therapeutically effective as late as 72 hours after infection. The wide range of reactivity probably relates to the infection history of the donor, whose plasmablasts generated antibodies with long regions that insert into the active site of the neuraminidase enzyme. Science , this issue p. 499

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

SARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future. One Sentence Summary: Antibody responses induced by natural mild-to-moderate SARS-CoV-2 infection are robust, neutralizing and are stable for at least 3 months.

Influenza virus infections remain a high risk to human health, causing up to 650,000 deaths worldwide every year, with an enormous burden on the health care system. Since currently available seasonal vaccines are only partially effective and often mismatched to the circulating strains, a broader protective influenza virus vaccine is needed.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.