Optimizing the breadth of SARS-CoV-2-neutralizing antibodies in vivo and in silico.

Since the emergence of SARS-CoV-2, the ongoing arms race between mutating viruses and human antibodies has revealed several novel strategies by which antibodies adapt to viral escape. While SARS-CoV-2 viruses exhibit high variability in epitopes targeted by neutralizing antibodies, certain epitopes remain conserved owing to their essential roles on viral fitness. Antibodies can acquire broadly neutralizing activity by targeting these vulnerable sites through affinity-based somatic evolution of immunoglobulin genes.

Antibody durability is influenced by interleukin-2 production by undifferentiated memory T helper cells and extensive B cell clonal expansion.

SARS-CoV-2-neutralizing antibody titers serve as immune correlates of protection against COVID-19; however, the durability varies among vaccinees. Here, we demonstrate that the durability of vaccine-boosted antibody responses is closely correlated with the pre-booster capacity of spike-reactive CD4 T cells to produce interleukin (IL)-2 and T helper type 2 (Th2) cytokines. IL-2 production by CD4 T cells was also associated with extensive B cell clonal expansion, which preceded the durable antibody responses.

Calboxyvinyl polymer adjuvant enhances respiratory iga responses through mucosal and systemic administration.

Adjuvants play a crucial role in enhancing vaccine efficacy. Although several adjuvants have been approved, there remains a demand for safer and more effective adjuvants for nasal vaccines. Here, we identified calboxyvinyl polymer (CVP) as a superior mucosal vaccine adjuvant from pharmaceutical base materials using our screening systems; single nasal vaccination of the CVP-combined influenza split vaccine-induced antigen-specific IgA and IgG antibodies and provided protection against lethal influenza virus infection.

Atypical memory B cells from natural malaria infection produced broadly neutralizing antibodies against Plasmodium vivax variants.

Expansion of atypical memory B cells (aMBCs) was demonstrated in malaria-exposed individuals. To date, the generation of P. vivax-specific aMBCs and their function in protective humoral immune responses is unknown.

Repeated Omicron exposures redirect SARS-CoV-2-specific memory B cell evolution toward the latest variants.

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.

Post-fusion influenza vaccine adjuvanted with SA-2 confers heterologous protection via Th1-polarized, non-neutralizing antibody responses.

Development of a universal influenza vaccine that can provide robust and long-lasting protection against heterologous infections is a global public health priority. A variety of vaccine antigens are designed to increase the antigenicity of conserved epitopes to elicit cross-protective antibodies that often lack virus-neutralizing activity. Given the contribution of antibody effector functions to cross-protection, adjuvants need to be added to modulate antibody effector functions as well as to enhance antibody quantity.

CD62L expression marks SARS-CoV-2 memory B cell subset with preference for neutralizing epitopes.

Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (B) cells have variation in the neutralizing activities. Here, by combining single B cell profiling with antibody functional assessment, we dissected the phenotype of B cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals.

Multimodal single-cell analyses of peripheral blood mononuclear cells of COVID-19 patients in Japan.

SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood.

Humoral immunity for durable control of SARS-CoV-2 and its variants.

The coronavirus disease 2019 (COVID-19) pandemic is ongoing because of the repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, highlighting the importance of developing vaccines for variants that may continue to emerge. In the present review, we discuss humoral immune responses against SARS-CoV-2 with a focus on the antibody breadth to the variants. Recent studies have revealed that the temporal maturation of humoral immunity improves the antibody potency and breadth to the variants after infection or vaccination.

SARS-CoV-2-specific CD4 T cell longevity correlates with Th17-like phenotype.

Determinants of memory T cell longevity following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain unknown. In addition, phenotypes associated with memory T cell longevity, antibody titers, and disease severity are incompletely understood. Here, we longitudinally analyzed SARS-CoV-2-specific T cell and antibody responses of a unique cohort with similar numbers of mild, moderate, and severe coronavirus disease 2019 cases.

Safety and immunogenicity of the Pfizer/BioNTech SARS-CoV-2 mRNA third booster vaccine dose against the BA.1 and BA.2 Omicron variants.

Background: The Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in Japan in November 2021. This variant contains up to 36 mutations in the spike protein, the target of neutralizing antibodies, and can escape vaccine-induced immunity. A booster vaccination campaign began with healthcare workers and high-risk groups.

Distinct immune cell dynamics correlate with the immunogenicity and reactogenicity of SARS-CoV-2 mRNA vaccine.

Two doses of Pfizer/BioNTech BNT162b2 mRNA vaccine elicit robust severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies with frequent adverse events. Here, by applying a high-dimensional immune profiling on 92 vaccinees, we identify six vaccine-induced immune dynamics that correlate with the amounts of neutralizing antibodies, the severity of adverse events, or both. The early dynamics of natural killer (NK)/monocyte subsets (CD16 NK cells, CD56 NK cells, and non-classical monocytes), dendritic cell (DC) subsets (DC3s and CD11c Axl Siglec-6 [AS]-DCs), and NKT-like cells are revealed as the distinct cell correlates for neutralizing-antibody titers, severity of adverse events, and both, respectively.