Pamuk Bilsel - Academia.edu (original) (raw)

Papers by Pamuk Bilsel

Research paper thumbnail of Mucosal immunization with dual influenza/COVID-19 single-replication virus vector protects hamsters from SARS-CoV-2 challenge

Research paper thumbnail of 10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

Open Forum Infectious Diseases, Nov 1, 2021

humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group ... more humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group compared to Control group. Solicited adverse events (AEs) until D7 post-vaccination and unsolicited AEs until D30 post-vaccination were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected through 12 months post-RZV dose 2. Immunogenicity was performed in the per-protocol set (PPS) and safety analyses in the exposed set. Results. Of 912 vaccinated adults, 863 were included in PPS (Co-Ad: 427; Control: 436). VRR for anti-glycoprotein E antibody concentrations was 99.1% in Co-Ad group. The predefined non-inferiority criteria for the humoral immune responses to RZV and PCV13 were met (Table 1). The overall frequency of solicited local AEs after RZV and PCV13 was comparable between Co-Ad and Control groups. Pain was the most common solicited local AE (Figure 1). The frequency of solicited general AEs was similar for the 1st RZV dose when co-administered with PCV13 or alone (57.4% vs 54.6%). Myalgia and fatigue were the most common solicited general AEs (Figure 2). The frequency (Co-Ad: 21.2%; Control: 23.1%) and nature of unsolicited AEs were balanced between groups. None of the reported SAEs, fatal SAEs, or pIMDs were vaccine-related.

Research paper thumbnail of Generation of a stably attenuated influenza virus by reverse genetics

Research paper thumbnail of Influenza A virus infection‐induced macroautophagy facilitates MHC class II‐restricted endogenous presentation of an immunodominant viral epitope

FEBS Journal, Dec 18, 2020

Influenza A virus infection-induced macroautophagy facilitates MHC class IIrestricted endogenous ... more Influenza A virus infection-induced macroautophagy facilitates MHC class IIrestricted endogenous presentation of an immunodominant viral epitope

Research paper thumbnail of Phosphoprotein andNucleocapsid Protein Evolution ofVesicular Stomatitis VirusNewJersey

Research paper thumbnail of Single-replication BM2SR vaccine provides sterilizing immunity and cross-lineage influenza B virus protection in mice

Vaccine, Jul 1, 2019

Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant mor... more Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant morbidity and mortality. There are two antigenically distinct lineages of influenza B virus, Yamagata lineage (YL) and Victoria lineage (VL). Since both B lineages have been co-circulating for years, more than 70% of influenza vaccines currently manufactured are quadrivalent consisting of influenza A (H1N1), influenza A (H3N2), influenza B (YL) and influenza B (VL) antigens. Although quadrivalent influenza vaccines tend to elevate immunity to both influenza B lineages, estimated overall vaccine efficacy against influenza B is still only around 42%. Thus, a more effective influenza B vaccine is needed. To meet this need, we generated BM2-deficient, single-replication (BM2SR) influenza B vaccine viruses that encode surface antigens from influenza B/Wisconsin/01/2010 (B/WI01, YL) and B/ Brisbane/60/2008 (B/Bris60, VL) viruses. The BM2SR-WI01 and BM2SR-Bris60 vaccine viruses are replication-deficient in vitro and in vivo, and can only replicate in a cell line that expresses the complementing BM2 protein. Both BM2SR viruses were non-pathogenic to mice, and vaccinated animals showed elevated mucosal and serum antibody responses to both Yamagata and Victoria lineages in addition to cellular responses. Serum antibody responses included lineage-specific hemagglutinin inhibition antibody (HAI) responses as well as responses to the stem region of the

Research paper thumbnail of Novel influenza vaccine M2SR protects against drifted H1N1 and H3N2 influenza virus challenge in ferrets with pre-existing immunity

Research paper thumbnail of Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge

Vaccines, Apr 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants

Vaccines

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death,... more Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, wh...

Research paper thumbnail of Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge

Vaccines

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly ci... more Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provide...

Research paper thumbnail of Longevity and Mechanism of Heterosubtypic Protection Induced by M2SR (M2-Deficient Single-Replication) Live Influenza Virus Vaccine in Mice

Vaccines

Seasonal influenza and the threat of global pandemics present a continuing threat to public healt... more Seasonal influenza and the threat of global pandemics present a continuing threat to public health. However, conventional inactivated influenza vaccines (IAVs) provide little cross-protective immunity and suboptimal efficacy, even against well-matched strains. Furthermore, the protection against matched strains has been shown to be of a short duration in both mouse models and humans. M2SR (M2-deficient single-replication influenza virus) is a single-replication vaccine that has been shown to provide effective cross-protection against heterosubtypic influenza viruses in both mouse and ferret models. In the present study, we investigated the duration and mechanism of heterosubtypic protection induced by M2SR in a mouse model. We previously showed that M2SR generated from influenza A/Puerto Rico/8/34 (H1N1) significantly protected C57BL/6 mice against lethal challenge with both influenza A/Puerto Rico/8/34 (H1N1, homosubtypic) and influenza A/Aichi/2/1968 (H3N2, heterosubtypic), wherea...

Research paper thumbnail of Intranasal M2SR (M2-Deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies in Adults

The Journal of Infectious Diseases

Background We previously demonstrated that an intranasal dose of 108 50% tissue culture infectiou... more Background We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection. Methods Serosusceptible subjects aged 18–49 years were randomized to receive 2 doses (108–109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines. Results The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%–56....

Research paper thumbnail of M2SR: A robust flu vaccine with long-lasting, cross-protective immunity

Journal of Vaccines and Vaccination, Oct 28, 2014

Research paper thumbnail of M2SR, a single replication universal flu vaccine

Virology & Mycology, Jul 24, 2015

Research paper thumbnail of Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults

Vaccines

M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protect... more M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo...

Research paper thumbnail of Designing effective flu vaccines against a broad-spectrum of influenza viruses

Virology & Mycology, Jul 24, 2015

Research paper thumbnail of 10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

Open Forum Infectious Diseases, 2021

Background Quadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs)... more Background Quadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs) against the viral hemagglutinin (HA). Despite annual update of HA vaccine antigens to match circulating strains, current vaccines provide ~60% vaccine effectiveness (VE). QIV VE can be as low as 10% when circulating strains do not match vaccine HA. The live M2SR (M2-deficient single replication) influenza vaccine candidate has previously shown broad humoral, mucosal and cellular immune responses and protection against multiple influenza A subtypes. Here we show similar properties with the Quadrivalent M2SR (Quad M2SR) against drifted influenza B challenge in comparison to QIV. Methods Ferrets pre-infected with influenza H1N1 and B/Yamagata viruses, were immunized intranasally (IN) with PBS (Mock) or Quad M2SR, or intramuscularly with Fluzone QIV. Serum collected post-vaccination was evaluated for Ab responses. Forty-two days after vaccination, ferrets were challenged IN with 106 pfu of ...

Research paper thumbnail of Generation of a stably attenuated influenza virus by reverse genetics

Research paper thumbnail of with Reduced Immunogenicity Rationally Engineered Therapeutic Proteins

Research paper thumbnail of M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain

The Journal of Infectious Diseases, 2021

Background Current influenza vaccines are strain specific and demonstrate low vaccine efficacy ag... more Background Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector immune response. Methods A phase 2 challenge study was conducted to assess the efficacy of an M2SR vaccine expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (Bris2007 M2SR H3N2; clade 1). Four weeks after vaccination, recipients were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b) and assessed for infection and clinical symptoms. Results Adverse events after vaccination were mild and similar in frequency for placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR recipients were infected after challenge, com...

Research paper thumbnail of Mucosal immunization with dual influenza/COVID-19 single-replication virus vector protects hamsters from SARS-CoV-2 challenge

Research paper thumbnail of 10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

Open Forum Infectious Diseases, Nov 1, 2021

humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group ... more humoral responses to RZV (1 month post-RZV dose 2) and PCV13 (1 month post-PCV13) in Co-Ad group compared to Control group. Solicited adverse events (AEs) until D7 post-vaccination and unsolicited AEs until D30 post-vaccination were recorded. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected through 12 months post-RZV dose 2. Immunogenicity was performed in the per-protocol set (PPS) and safety analyses in the exposed set. Results. Of 912 vaccinated adults, 863 were included in PPS (Co-Ad: 427; Control: 436). VRR for anti-glycoprotein E antibody concentrations was 99.1% in Co-Ad group. The predefined non-inferiority criteria for the humoral immune responses to RZV and PCV13 were met (Table 1). The overall frequency of solicited local AEs after RZV and PCV13 was comparable between Co-Ad and Control groups. Pain was the most common solicited local AE (Figure 1). The frequency of solicited general AEs was similar for the 1st RZV dose when co-administered with PCV13 or alone (57.4% vs 54.6%). Myalgia and fatigue were the most common solicited general AEs (Figure 2). The frequency (Co-Ad: 21.2%; Control: 23.1%) and nature of unsolicited AEs were balanced between groups. None of the reported SAEs, fatal SAEs, or pIMDs were vaccine-related.

Research paper thumbnail of Generation of a stably attenuated influenza virus by reverse genetics

Research paper thumbnail of Influenza A virus infection‐induced macroautophagy facilitates MHC class II‐restricted endogenous presentation of an immunodominant viral epitope

FEBS Journal, Dec 18, 2020

Influenza A virus infection-induced macroautophagy facilitates MHC class IIrestricted endogenous ... more Influenza A virus infection-induced macroautophagy facilitates MHC class IIrestricted endogenous presentation of an immunodominant viral epitope

Research paper thumbnail of Phosphoprotein andNucleocapsid Protein Evolution ofVesicular Stomatitis VirusNewJersey

Research paper thumbnail of Single-replication BM2SR vaccine provides sterilizing immunity and cross-lineage influenza B virus protection in mice

Vaccine, Jul 1, 2019

Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant mor... more Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant morbidity and mortality. There are two antigenically distinct lineages of influenza B virus, Yamagata lineage (YL) and Victoria lineage (VL). Since both B lineages have been co-circulating for years, more than 70% of influenza vaccines currently manufactured are quadrivalent consisting of influenza A (H1N1), influenza A (H3N2), influenza B (YL) and influenza B (VL) antigens. Although quadrivalent influenza vaccines tend to elevate immunity to both influenza B lineages, estimated overall vaccine efficacy against influenza B is still only around 42%. Thus, a more effective influenza B vaccine is needed. To meet this need, we generated BM2-deficient, single-replication (BM2SR) influenza B vaccine viruses that encode surface antigens from influenza B/Wisconsin/01/2010 (B/WI01, YL) and B/ Brisbane/60/2008 (B/Bris60, VL) viruses. The BM2SR-WI01 and BM2SR-Bris60 vaccine viruses are replication-deficient in vitro and in vivo, and can only replicate in a cell line that expresses the complementing BM2 protein. Both BM2SR viruses were non-pathogenic to mice, and vaccinated animals showed elevated mucosal and serum antibody responses to both Yamagata and Victoria lineages in addition to cellular responses. Serum antibody responses included lineage-specific hemagglutinin inhibition antibody (HAI) responses as well as responses to the stem region of the

Research paper thumbnail of Novel influenza vaccine M2SR protects against drifted H1N1 and H3N2 influenza virus challenge in ferrets with pre-existing immunity

Research paper thumbnail of Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge

Vaccines, Apr 4, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants

Vaccines

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death,... more Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, wh...

Research paper thumbnail of Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge

Vaccines

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly ci... more Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provide...

Research paper thumbnail of Longevity and Mechanism of Heterosubtypic Protection Induced by M2SR (M2-Deficient Single-Replication) Live Influenza Virus Vaccine in Mice

Vaccines

Seasonal influenza and the threat of global pandemics present a continuing threat to public healt... more Seasonal influenza and the threat of global pandemics present a continuing threat to public health. However, conventional inactivated influenza vaccines (IAVs) provide little cross-protective immunity and suboptimal efficacy, even against well-matched strains. Furthermore, the protection against matched strains has been shown to be of a short duration in both mouse models and humans. M2SR (M2-deficient single-replication influenza virus) is a single-replication vaccine that has been shown to provide effective cross-protection against heterosubtypic influenza viruses in both mouse and ferret models. In the present study, we investigated the duration and mechanism of heterosubtypic protection induced by M2SR in a mouse model. We previously showed that M2SR generated from influenza A/Puerto Rico/8/34 (H1N1) significantly protected C57BL/6 mice against lethal challenge with both influenza A/Puerto Rico/8/34 (H1N1, homosubtypic) and influenza A/Aichi/2/1968 (H3N2, heterosubtypic), wherea...

Research paper thumbnail of Intranasal M2SR (M2-Deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies in Adults

The Journal of Infectious Diseases

Background We previously demonstrated that an intranasal dose of 108 50% tissue culture infectiou... more Background We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection. Methods Serosusceptible subjects aged 18–49 years were randomized to receive 2 doses (108–109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines. Results The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%–56....

Research paper thumbnail of M2SR: A robust flu vaccine with long-lasting, cross-protective immunity

Journal of Vaccines and Vaccination, Oct 28, 2014

Research paper thumbnail of M2SR, a single replication universal flu vaccine

Virology & Mycology, Jul 24, 2015

Research paper thumbnail of Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults

Vaccines

M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protect... more M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (106, 107 or 108 tissue culture infectious dose (TCID50)) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo...

Research paper thumbnail of Designing effective flu vaccines against a broad-spectrum of influenza viruses

Virology & Mycology, Jul 24, 2015

Research paper thumbnail of 10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

Open Forum Infectious Diseases, 2021

Background Quadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs)... more Background Quadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs) against the viral hemagglutinin (HA). Despite annual update of HA vaccine antigens to match circulating strains, current vaccines provide ~60% vaccine effectiveness (VE). QIV VE can be as low as 10% when circulating strains do not match vaccine HA. The live M2SR (M2-deficient single replication) influenza vaccine candidate has previously shown broad humoral, mucosal and cellular immune responses and protection against multiple influenza A subtypes. Here we show similar properties with the Quadrivalent M2SR (Quad M2SR) against drifted influenza B challenge in comparison to QIV. Methods Ferrets pre-infected with influenza H1N1 and B/Yamagata viruses, were immunized intranasally (IN) with PBS (Mock) or Quad M2SR, or intramuscularly with Fluzone QIV. Serum collected post-vaccination was evaluated for Ab responses. Forty-two days after vaccination, ferrets were challenged IN with 106 pfu of ...

Research paper thumbnail of Generation of a stably attenuated influenza virus by reverse genetics

Research paper thumbnail of with Reduced Immunogenicity Rationally Engineered Therapeutic Proteins

Research paper thumbnail of M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain

The Journal of Infectious Diseases, 2021

Background Current influenza vaccines are strain specific and demonstrate low vaccine efficacy ag... more Background Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector immune response. Methods A phase 2 challenge study was conducted to assess the efficacy of an M2SR vaccine expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (Bris2007 M2SR H3N2; clade 1). Four weeks after vaccination, recipients were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b) and assessed for infection and clinical symptoms. Results Adverse events after vaccination were mild and similar in frequency for placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR recipients were infected after challenge, com...