SAN DIEGO – Influenza vaccines with four strains of the virus, rather than three, showed promise in a trio of clinical trials.
The investigational "quadrivalent" vaccines act against two strains of influenza A, as do current trivalent drugs, but they also have antigens against two strains of influenza B, as opposed to one, researchers told an oral session at the annual IDWeek meeting here.
The two quadrivalent vaccines under study are being developed by different pharmaceutical makers and the studies presented different aspects of immunogenicity and safety.
The three studies were conducted among children under 9, adults 18 and older, and seniors 65 and older. Each study had three arms – the quadrivalent vaccine, a licensed trivalent vaccine, and a similar trivalent vaccine with the other B lineage.
The addition of the extra B strain should, in principle, avoid the vaccine mismatches that are now common, commented Timothy Uyeki, MD, of the CDC in Atlanta, who was not involved in any of the studies but who moderated the session where the findings were presented.
In the first study, combined results from three phase II/III studies showed that a quadrivalent vaccine had similar safety to standard trivalent vaccines, according to David Greenberg, MD, of Sanofi Pasteur of Swiftwater, Pa.
Overall, Greenberg reported, safety did not differ significantly among the vaccines.
And antibody responses to all four strains in the quadrivalent vaccine were not inferior to those prompted by the equivalent strains in the control trivalent vaccines.
But the antibody responses to the B strains in the quadrivalent vaccine were superior to those prompted by the control vaccine that did not contain the respective B strain, Greenberg reported.
Results were similar for a study of the other quad vaccine, this one manufactured by GlaxoSmithKline, according to Joanne Langley, MD, of Dalhousie University in Halifax, N.S.
Langley and colleagues tested the vaccine in 2,793 children ages 3 through 17, again comparing it with two trivalent control vaccines each containing one of the B lineages.
Again, safety was similar and immunogenicity of the quad vaccine was not inferior for the strains the vaccines had in common but superior for the B lineage missing from the respective control vaccines, Langley said.
In the remaining study, 5,168 children ages 3 through 8 were randomly vaccinated with GlaxoSmithKline's quad vaccine or with a hepatitis A vaccine before the 2010-2011 flu season in an effort to measure the vaccine efficacy.
Overall, the vaccine had an efficacy of 55.4% in preventing flu, according to Varsha Jain, MD, of GlaxoSmithKline in King of Prussia, Pa.
But against moderate to severe flu – defined as a fever of more than 39 degrees C or acute otitis media, signs of lower respiratory tract disease, or extra-pulmonary complications – vaccine efficacy was 73.08%, Jain reported.
Uyeki told MedPage Today that two main lineages of influenza B – dubbed Victoria and Yamagata – have been circulating for more than a decade. Choosing which one to include in the annual flu vaccine has been a guessing game that the new vaccines are intended to end, he said.
When current vaccines' B strain is mismatched against the circulating strain, there's little protection against influenza B, Uyeki said. "The thought is that by including both lineages you have more protection," Uyeki said.
While there is a perception that influenza B doesn't cause serious disease, that's not always true, he said. "In particular for children, influenza B virus infections are fairly substantial," he said.
Taken together, Uyeki said, there appear to be no differences in immunogenicity and safety between the quadrivalent and trivalent vaccines.
"There's no interference in the antibody response and there's no difference in safety compared with the trivalent vaccine, so all that is as we had hoped," he said.
What's needed now, he added, are more data on both efficacy and effectiveness compiled over several flu seasons.
The study by Greenberg, et al was supported by Sanofi Pasteur. Greenberg is an employee of the company.
The study by Jain, et al was supported by GlaxoSmithKline Biologicals. Jain is an employee of the company.
The study by Langley, et al was supported by GlaxoSmithKline Biologicals. Langley reported financial links with the company and several authors are employees.
Uyeki made no disclosures.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Infectious Disease WeekSource Reference: Greenberg DP, et al "Report of three phase II/III clinical trials of quadrivalent inactivated influenza vaccine (QIV) containing two A and two B strains among children, adults, and seniors" IDWeek 2012.
Infectious Disease WeekSource Reference: Jain VK, et al "Efficacy of an inactivated quadrivalent influenza vaccine candidate, in children 3 to 8 years of age" IDWeek 2012.
Infectious Disease WeekSource Reference: Langley JM, et al "Immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate: a randomized controlled trial in children" IDWeek 2012.