Restrained expansion of the recall germinal center response as biomarker of protection for influenza vaccination in mice.

Correlates of protection (CoP) are invaluable for iterative vaccine design studies, especially in pursuit of complex vaccines such as a universal influenza vaccine (UFV) where a single antigen is optimized to elicit broad protection against many viral antigenic variants. Since broadly protective antibodies against influenza virus often exhibit mutational evidence of prolonged diversification, we studied germinal center (GC) kinetics in hemagglutinin (HA) immunized mice. Here we report that as early as 4 days after secondary immunization, the expansion of HA-specific GC B cells inversely correlated to protection against influenza virus challenge, induced by the antigen. In contrast, follicular T helper (TFH) cells did not expand differently after boost vaccination, suggestive of a B-cell intrinsic difference in activation and differentiation inferred by protective antigen properties. Importantly, differences in antigen dose only affected GC B-cell frequencies after primary immunization. The absence of accompanying differences in total anti-HA or epitope-specific antibody levels induced by vaccines of different efficacy suggests that the GC B-cell response upon revaccination represents an early and unique marker of protection that may significantly accelerate the pre-clinical phase of vaccine development

Mini-hemagglutinin vaccination induces cross-reactive antibodies in pre-exposed NHP that protect mice against lethal influenza challenge

Seasonal vaccines are currently the most effective countermeasure against influenza. However, seasonal vaccines are only effective against strains closely related to the influenza strains contained in the vaccine. Recently a new hemagglutinin (HA) stem-based antigen, the so-called "mini-HA", has been shown to induce a cross-protective immune response in influenza-naive mice and non-human primates (NHP). However, prior exposure to influenza can have a profound effect on the immune response to subsequent influenza infection and the protective efficacy of vaccination. Here we show that mini-HA, compared to a trivalent influenza vaccine (TIV), elicits a broadened influenza-specific humoral immune response in NHP previously exposed to influenza. Serum transfer experiments showed that antibodies induced by both mini-HA and seasonal vaccine protected mice against lethal challenge with a H1N1 influenza strain heterologous to the H1 HA included in the TIV. However, antibodies elicited by mini-HA showed an additional benefit of protecting mice against lethal heterosubtypic H5N1 influenza challenge, associated with H5 HA-specific functional antibodies

Booster with Ad26.COV2.S or Omicron-adapted vaccine enhanced immunity and efficacy against SARS-CoV-2 Omicron in macaques

Variant booster vaccines are a strategy to improve protection against SARS-CoV-2. Here, the authors find that both Wuhan-Hu-1-based Ad26.COV2.S or an Omicron-adapted booster vaccine provide robust immune responses and protection against Omicron in NHP