Perspective

Novel flu vaccine shows efficacy against mismatched H3N2 virus

Adrian Wildfire
Adrian Wildfire

Preliminary phase 2 data from a controlled human infection trial showed that an investigational influenza vaccine being developed by FluGen was protective against a substantially mismatched influenza A(H3N2) virus, the company announced.

The vaccine, M2SR, showed efficacy against an H3N2 A/Belgium challenge agent developed by SGS. FluGen said the mismatch between M2SR and the challenge virus was greater than what was seen in 2014-2015, when the seasonal influenza vaccine was estimated to be just 6% effective against significantly drifted H3N2 viruses.

“Our goal in manufacturing a novel, nonhemagglutinating, influenza A (H3N2) strain to use as a challenge agent was to improve current disease modelling and help research efforts to combat the very real threat that is posed by the influenza virus to global populations,” SGS scientific director Adrian Wildfire said in a news release.

Choosing an H3N2 component for seasonal influenza vaccines is a challenge because the strain is more prone to mutation than other influenza viruses, such as H1N1. Including an appropriate H3N2 component in the seasonal influenza vaccine is seen as critical because the virus tends to cause relatively severe illness, and high-H3N2 seasons tend to have high rates of hospitalizations and death.

H3N2 was the predominant circulating virus during last year’s severe influenza season, in which an estimated 900,000 people were hospitalized and 80,000 died. This season’s vaccine included a different H3N2 component that performed better against recent viruses. Recently, WHO delayed choosing an H3N2 vaccine virus for 2019-2020, opting to wait for more data.

According to the release, the study included 99 healthy adults who were randomly assigned to receive a placebo or a single intranasal dose of the M2SR vaccine. They were then exposed to the A/Belgium challenge agent, and researchers assessed for vaccine safety, viral shedding and relevant clinical symptoms. Researchers will follow the subjects for 4 months after the challenge. The study is expected to be completed by the second quarter of 2019.

“As the aim of the vaccine design was to promote both T and B cell responses, we were hoping to see reductions in disease parameters such as influenza-like symptoms as well as falls in the viral Area Under the Curve,” Wildfire told Infectious Disease News.

More than half of participants who received the investigational vaccine demonstrated a serum antibody response to M2SR, Wildfire noted. Among them, there was a 34% reduction of viral load during the challenge phase of the study compared with placebo. Researchers also observed a 62% reduction in viral load among trial participants who developed antibody to the vaccine and challenge virus, according to FluGen.

“Certainly, this approach offers hope to the desperate situation we have seen over the past 5 to 10 years where total H3N2 vaccine efficacy — vaccine efficacy for all age groups — has been as low as 15% and below 10% for the elderly year on year,” Wildfire said. – by Marley Ghizzone

Disclosure: Wildfire is employed by SGS.

Adrian Wildfire
Adrian Wildfire

Preliminary phase 2 data from a controlled human infection trial showed that an investigational influenza vaccine being developed by FluGen was protective against a substantially mismatched influenza A(H3N2) virus, the company announced.

The vaccine, M2SR, showed efficacy against an H3N2 A/Belgium challenge agent developed by SGS. FluGen said the mismatch between M2SR and the challenge virus was greater than what was seen in 2014-2015, when the seasonal influenza vaccine was estimated to be just 6% effective against significantly drifted H3N2 viruses.

“Our goal in manufacturing a novel, nonhemagglutinating, influenza A (H3N2) strain to use as a challenge agent was to improve current disease modelling and help research efforts to combat the very real threat that is posed by the influenza virus to global populations,” SGS scientific director Adrian Wildfire said in a news release.

Choosing an H3N2 component for seasonal influenza vaccines is a challenge because the strain is more prone to mutation than other influenza viruses, such as H1N1. Including an appropriate H3N2 component in the seasonal influenza vaccine is seen as critical because the virus tends to cause relatively severe illness, and high-H3N2 seasons tend to have high rates of hospitalizations and death.

H3N2 was the predominant circulating virus during last year’s severe influenza season, in which an estimated 900,000 people were hospitalized and 80,000 died. This season’s vaccine included a different H3N2 component that performed better against recent viruses. Recently, WHO delayed choosing an H3N2 vaccine virus for 2019-2020, opting to wait for more data.

According to the release, the study included 99 healthy adults who were randomly assigned to receive a placebo or a single intranasal dose of the M2SR vaccine. They were then exposed to the A/Belgium challenge agent, and researchers assessed for vaccine safety, viral shedding and relevant clinical symptoms. Researchers will follow the subjects for 4 months after the challenge. The study is expected to be completed by the second quarter of 2019.

“As the aim of the vaccine design was to promote both T and B cell responses, we were hoping to see reductions in disease parameters such as influenza-like symptoms as well as falls in the viral Area Under the Curve,” Wildfire told Infectious Disease News.

More than half of participants who received the investigational vaccine demonstrated a serum antibody response to M2SR, Wildfire noted. Among them, there was a 34% reduction of viral load during the challenge phase of the study compared with placebo. Researchers also observed a 62% reduction in viral load among trial participants who developed antibody to the vaccine and challenge virus, according to FluGen.

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“Certainly, this approach offers hope to the desperate situation we have seen over the past 5 to 10 years where total H3N2 vaccine efficacy — vaccine efficacy for all age groups — has been as low as 15% and below 10% for the elderly year on year,” Wildfire said. – by Marley Ghizzone

Disclosure: Wildfire is employed by SGS.

    Perspective
    William Schaffner

    William Schaffner

    Both patients and providers yearn for a more effective influenza vaccine. The limitations of the currently available vaccines are known only too well: the degree of match between the antigens in the vaccine and the circulating influenza viruses may be uncertain; even at its best, the effectiveness of the vaccines is not optimal; egg-based production appears to impair the specificity of protection; and the duration of protection in frail patients may wane. In response, we have seen the licensure of quadrivalent, high-dose, adjuvanted, cell-based and recombinant vaccines — all efforts to improve the annual vaccines’ effectiveness.

    And the research continues. This is an early report of an intriguing vaccine candidate. The vaccine is a live H3N2 virus that has been molecularly engineered so that it can complete only a single replication cycle after it has been sprayed into the nose (extraordinary!). In a placebo–controlled human challenge study (also extraordinary!), volunteers were exposed to a mismatched, drifted H3N2 influenza virus. The company reports that “findings are very positive” regarding immunogenicity, effectiveness and safety. We look forward to seeing the actual data and wish them well in the further development and evaluation of this novel vaccine candidate. Hope springs eternal … and long journeys begin with first steps.

    • William Schaffner, MD
    • Infectious Disease News Editorial Board member
      Professor of preventive medicine,
      Vanderbilt University Medical Center
      Medical director,
      National Foundation for Infectious Diseases

    Disclosures: Schaffner reports being on a data safety monitoring board for Pfizer, being a consultant for Dynavax, Roche, Seqirus, Shionogi and SutroVax, and serving as a past member on a data safety monitoring board for Merck.