Researchers ‘encouraged’ by early data from universal flu vaccine study

Peter Palese, PhD 
Peter Palese
Florian Krammer, PhD 
Florian Krammer

Researchers were “encouraged” by the interim results from a phase 1 study of a novel influenza vaccine approach they hope will one day protect patients from both seasonal and pandemic influenza.

They tested the ability of chimeric hemagglutinin (cHA)-based universal influenza vaccine candidates to target the conserved stalk of hemagglutinin surface proteins, rather than the globular head.

“We are very encouraged that the preliminary data are compelling in terms of inducing a protective and long-lasting immune response in humans,” Peter Palese, PhD, professor and chair of the department of microbiology at the Icahn School of Medicine at Mount Sinai in New York, told Infectious Disease News.

The head of the hemagglutinin — which binds influenza viruses to human hosts cells and is targeted by current vaccines — mutates frequently, leading to an almost yearly need to update the composition of seasonal vaccines. On the other hand, the stalk remains more or less stable.

Infographic about vaccine effectiveness by season (updated) 
 

Palese and colleagues conducted a randomized, observer-blinded multicenter phase 1 study among healthy adults aged 18 to 39 years. They tested three regimens: a chimeric H8/1 hemagglutinin-based live-attenuated vaccine (LAIV), followed by a boost with a nonadjuvanted chimeric H5/1 hemagglutinin-based inactivated 3 vaccine (IIV); the same regimen but the IIV included an adjuvant called AS03; and a prime-boost regimen that included an adjuvanted cH8/1 IIV prime, followed by an adjuvanted cH5/1 IIV boost.

After the prime, the adjuvanted IIV induced a significant serum immunoglobulin G antibody response, as well as a sevenfold increase in anti-H1 stalk titers. The same results were not observed with the LAIV.
Post-boost, all of the regimens induced detectable H1 stalk, cross-reactive serum IgG antibody and peripheral blood plasmablast responses, Palese and colleagues reported. Specifically, they observed a 2.2- to 5.6-fold induction in anti-H1 stalk antibody titers over baseline.

The researchers said the results support further development of the adjuvanted IIV vaccine candidate “as part of a universal influenza virus vaccine strategy.”

“We are currently in phase 1 trials; it would take phase 2 and then phase 3 trials — of a yet unspecified design — to bring this to the market,” Florian Krammer, PhD, professor of microbiology at the Icahn School of Medicine at Mount Sinai, told Infectious Disease News.

According to a news release, the vaccine candidate was found to be cross-reactive for both currently circulating human influenza virus and avian and bat influenza virus subtypes. Moreover, with only the prime, the inactivated formula induced a “very strong anti-stalk response,” which Krammer said indicates possible protection against pandemic strains with only one vaccination.

“In order to make this approach an FDA-approved vaccine, successful phase 2 and phase 3 trials are necessary and that requires money, money, money,” Palese said.

In a related comment, Sophie A. Valkenburg, BioMedSci, BSci, DPhil, and Benjamin J. Cowling, PhD, both from the University of Hong Kong, noted that the field studying universal influenza vaccine candidates is expanding.

“Lessons will be learnt from each trial — the development of a broadly protective universal influenza vaccine will be an iterative process to optimize design and strategy — but these trials show encouraging progress on the path towards universal influenza vaccines,” they wrote. – by Marley Ghizzone

References:

Bernstein DI, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30393-7.

Disclosures: Krammer and Palese report being named as inventors on patents issued and filed by the Icahn School of Medicine at Mount Sinai covering the used of chimeric haemagglutinin antigens as vaccines. Please see the study for all other authors’ relevant financial disclosures. Cowling reports receiving honoraria from Sanofi Pasteur and Roche. Valkenburg reports no relevant financial disclosures.

Peter Palese, PhD 
Peter Palese
Florian Krammer, PhD 
Florian Krammer

Researchers were “encouraged” by the interim results from a phase 1 study of a novel influenza vaccine approach they hope will one day protect patients from both seasonal and pandemic influenza.

They tested the ability of chimeric hemagglutinin (cHA)-based universal influenza vaccine candidates to target the conserved stalk of hemagglutinin surface proteins, rather than the globular head.

“We are very encouraged that the preliminary data are compelling in terms of inducing a protective and long-lasting immune response in humans,” Peter Palese, PhD, professor and chair of the department of microbiology at the Icahn School of Medicine at Mount Sinai in New York, told Infectious Disease News.

The head of the hemagglutinin — which binds influenza viruses to human hosts cells and is targeted by current vaccines — mutates frequently, leading to an almost yearly need to update the composition of seasonal vaccines. On the other hand, the stalk remains more or less stable.

Infographic about vaccine effectiveness by season (updated) 
 

Palese and colleagues conducted a randomized, observer-blinded multicenter phase 1 study among healthy adults aged 18 to 39 years. They tested three regimens: a chimeric H8/1 hemagglutinin-based live-attenuated vaccine (LAIV), followed by a boost with a nonadjuvanted chimeric H5/1 hemagglutinin-based inactivated 3 vaccine (IIV); the same regimen but the IIV included an adjuvant called AS03; and a prime-boost regimen that included an adjuvanted cH8/1 IIV prime, followed by an adjuvanted cH5/1 IIV boost.

After the prime, the adjuvanted IIV induced a significant serum immunoglobulin G antibody response, as well as a sevenfold increase in anti-H1 stalk titers. The same results were not observed with the LAIV.
Post-boost, all of the regimens induced detectable H1 stalk, cross-reactive serum IgG antibody and peripheral blood plasmablast responses, Palese and colleagues reported. Specifically, they observed a 2.2- to 5.6-fold induction in anti-H1 stalk antibody titers over baseline.

The researchers said the results support further development of the adjuvanted IIV vaccine candidate “as part of a universal influenza virus vaccine strategy.”

“We are currently in phase 1 trials; it would take phase 2 and then phase 3 trials — of a yet unspecified design — to bring this to the market,” Florian Krammer, PhD, professor of microbiology at the Icahn School of Medicine at Mount Sinai, told Infectious Disease News.

According to a news release, the vaccine candidate was found to be cross-reactive for both currently circulating human influenza virus and avian and bat influenza virus subtypes. Moreover, with only the prime, the inactivated formula induced a “very strong anti-stalk response,” which Krammer said indicates possible protection against pandemic strains with only one vaccination.

PAGE BREAK

“In order to make this approach an FDA-approved vaccine, successful phase 2 and phase 3 trials are necessary and that requires money, money, money,” Palese said.

In a related comment, Sophie A. Valkenburg, BioMedSci, BSci, DPhil, and Benjamin J. Cowling, PhD, both from the University of Hong Kong, noted that the field studying universal influenza vaccine candidates is expanding.

“Lessons will be learnt from each trial — the development of a broadly protective universal influenza vaccine will be an iterative process to optimize design and strategy — but these trials show encouraging progress on the path towards universal influenza vaccines,” they wrote. – by Marley Ghizzone

References:

Bernstein DI, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30393-7.

Disclosures: Krammer and Palese report being named as inventors on patents issued and filed by the Icahn School of Medicine at Mount Sinai covering the used of chimeric haemagglutinin antigens as vaccines. Please see the study for all other authors’ relevant financial disclosures. Cowling reports receiving honoraria from Sanofi Pasteur and Roche. Valkenburg reports no relevant financial disclosures.