Biology subjects

Muramatsu, H.

Publications and source records attributed to Muramatsu, H..

22 records · Page 2Linked to original sources

bioRxiv2022

Immunity to seasonal coronavirus spike proteins does not protect from SARS-CoV-2 challenge in a mouse model but has no detrimental effect on protection mediated by COVID-19 mRNA vaccination

Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses. In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection as compared to the negative controls. While a negligible back-boosting effect against betacoronavirus spike proteins was observed after SARS-CoV-2 infection, there was no negative original antigenic sin-like effect on the immune response and protection induced by SARS-CoV-2 mRNA vaccination in animals with pre-existing immunity to seasonal coronavirus spike proteins. ImportanceThe impact that immunity against seasonal coronaviruses has on both susceptibility to SARS-CoV-2 infection as well as on COVID-19 vaccination is unclear. This study provides insights into both questions in a mouse model of SARS-CoV-2.

microbiology↗

bioRxiv2022

Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization

The ability of serum antibody to protect against pathogens arises from the interplay of antigen-specific B cell clones of different affinities and fine specificities. These cellular dynamics are ultimately responsible for serum-level phenomena such as antibody imprinting or "Original Antigenic Sin" (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells that responded to a stimulus upon exposure to related antigens. Imprinting/OAS is thought to pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-2. Precise measurement of the extent to which imprinting/OAS inhibits the recruitment of new B cell clones by boosting is challenging because cellular and temporal origins cannot readily be assigned to antibodies in circulation. Thus, the extent to which imprinting/OAS impacts the induction of new responses in various settings remains unclear. To address this, we developed a "molecular fate-mapping" approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that, upon sequential homologous boosting, the serum antibody response strongly favors reuse of the first cohort of B cell clones over the recruitment of new, naIve-derived B cells. This "primary addiction" decreases as a function of antigenic distance, allowing secondary immunization with divergent influenza virus or SARS-CoV-2 glycoproteins to overcome imprinting/OAS by targeting novel epitopes absent from the priming variant. Our findings have implications for the understanding of imprinting/OAS, and for the design and testing of vaccines aimed at eliciting antibodies to evolving antigens.

immunology↗

bioRxiv2022

A universal influenza mRNA vaccine candidate boosts T-cell responses and reduces zoonotic influenza virus disease in ferrets

Universal influenza vaccines have the potential to protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell-inducing nucleoside-modified mRNA vaccine that encodes the conserved nucleoprotein, matrix protein 1 and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naive ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly-reactive T cells in the circulation, bone marrow and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins are a promising strategy to induce broadly-protective T-cell immunity against influenza viruses.

immunology↗

bioRxiv2022

Nucleoside-modified mRNA-based influenza vaccines circumvent problems associated with H3N2 vaccine strain egg-adaptation

Most human influenza vaccine antigens are produced in fertilized chicken eggs. Recent H3N2 egg-based vaccine antigens have limited effectiveness, partially due to egg-adaptive substitutions that alter the antigenicity of the hemagglutinin (HA) protein. The nucleoside-modified messenger RNA encapsulated in lipid nanoparticle (mRNA-LNP) vaccine platform is a promising alternative for egg-based influenza vaccines because mRNA-LNP-derived antigens are not subject to adaptive pressures that arise during the production of antigens in chicken eggs. Here, we compared H3N2-specific antibody responses in mice vaccinated with either 3c.2A H3-encoded mRNA-LNP or a conventional egg-based Fluzone vaccine (which included an egg-adapted 3c.2A antigen) supplemented with an MF59-like adjuvant. We tested mRNA-LNP encoding wild-type and egg-adapted 3c.2A H3 antigens. We found that mRNA-LNP encoding wild-type 3c.2A H3 elicited antibodies that neutralized the wild-type 3c.2A H3N2 virus more effectively relative to antibodies elicited by mRNA-LNP encoding egg-adapted 3c2.A H3 or the egg-based Fluzone vaccine. mRNA-LNP expressing either wild-type or egg-adapted 3c2.A H3 protected mice against infection with the wild-type 3c2.A H3N2, whereas the egg-based Fluzone vaccine did not. We found that both mRNA-LNP vaccines elicited high levels of group 2 HA stalk-reactive antibodies that likely contributed to protection in vivo. Our studies indicate that nucleoside-modified mRNA-LNP-based vaccines can circumvent problems associated with egg-adaptations with recent 3c2.A H3N2 viruses. SummaryThis study shows that the nucleoside-modified messenger RNA encapsulated in lipid nanoparticle (mRNA-LNP) vaccine platform is a promising alternative for egg-based influenza vaccines. We show that mRNA-LNP expressing H3 antigens elicit high levels of antibodies in mice and protect against H3N2 influenza virus infection.

microbiology↗