Recombinant Influenza Vaccine Safe, Effective Among Seniors

Nicola M. Parry, DVM

June 23, 2017

A quadrivalent, recombinant influenza vaccine (RIV4) is safe and provides better protection than a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) against influenza-like illness among adults aged 50 years or older, a new study shows.

The study results are very encouraging; however, the "absolute differences in laboratory-confirmed influenza infections between the RIV4 and the standard IIV4 were small," Walter A. Orenstein, MD, DSc (Hon), associate director of the Emory Vaccine Center and professor of medicine, pediatrics, and global health at Emory University, Atlanta, Georgia, told Medscape Medical News.

Lisa M. Dunkle, MD, from Protein Sciences, Meriden, Connecticut, and colleagues published the results of their study in the June 22 issue of the New England Journal of Medicine.

"The cumulative incidence of [reverse-transcriptase polymerase-chain-reaction (RT-PCR)]-confirmed influenza-like illness showed significant efficacy of RIV4 over IIV4 throughout the influenza season (hazard ratio, 0.69; 95% [confidence interval (CI)], 0.53 to 0.90; P=0.006)," the authors write.

During the 2014 to 2015 influenza season in the United States, circulating strains of influenza A(H3N2) viruses were antigenically and genetically different from the 2014 to 2015 vaccine strain.

This mismatch resulted in a lower than usual vaccine effectiveness in adults aged 50 years or older, and thus a higher than usual rate of influenza-associated hospitalizations among adults aged 65 years or older.

Better vaccines are needed to reduce the burden of influenza on public health, and the authors emphasize that using a recombinant vaccine could help achieve this goal.

The researchers conducted a randomized, double-blind, multicenter, phase 3-4 trial to compare the efficacy of RIV4 with IIV4 against influenza-like illness in older adults.

They enrolled 9003 adults who were 50 years of age or older and randomly assigned them to receive a single dose of either RIV4 or IIV4 at one of 40 outpatient centers across the United States. After vaccination, participants were asked to return to their trial site if they developed influenza-related respiratory symptoms (such as cough, sore throat, or difficulty breathing) or systemic symptoms (such as fever, chills, or myalgia).

Patients who had at least one symptom in both the respiratory and systemic illness categories underwent influenza testing. The researchers collected a nasopharyngeal swab from these patients within 72 hours after the onset of symptoms, and used RT-PCR and virus culture to confirm a diagnosis of influenza infection.

The full analysis included 8963 adults, and 8672 (96.8%) of these with postvaccination data made up the safety population.

The researchers performed a modified per protocol analysis, which included those participants who received trial vaccine and provided efficacy data at least 14 days later, with no major protocol deviations.

They also performed a post hoc analysis of a modified intention-to-treat population, which included all participants who were randomly assigned to receive trial vaccine and provided follow-up efficacy data at least 14 days later.

RT-PCR-confirmed influenza-like illness caused by any influenza strain, starting 14 days or more after vaccination, occurred in 96 (2.2%) of 4303 of participants who received RIV4, and in 138 (3.2%) of 4301 of those who received IIV4.

The modified per protocol analysis therefore showed that the probability of influenza-like illness occurring was 30% lower with RIV4 than with IIV4 (95% CI, 10% - 47%; P = .006).

The post hoc efficacy analysis showed that influenza-like illness occurred in 96 (2.2%) of 4427 of participants who received RIV4, and in 138 (3.1%) of 4428 of those who received IIV4.

The researchers also performed post hoc analyses of relative vaccine efficacy against influenza type A and type B. Although they found that RIV4 had a relative efficacy of 36% (95% CI, 14% - 53%; hazard ratio, 0.64 [95% CI, 0.48 - 0.86]; P = .003) against influenza A, they found no difference between the two vaccines against influenza B.

The safety profiles of the vaccines were also similar. Although 145 RIV4 recipients (3.4%) and 132 IIV4 recipients (3.0%) reported a serious adverse event within 6 months after vaccination, the authors state that all were events that occur commonly among older adults. Death occurred in eight RIV4 recipients and 12 IIV4 recipients. None of the deaths or other serious adverse events were considered to be study-related.

These findings show that RIV4 provided better protection than standard-dose IIV4 against laboratory-confirmed influenza-like illness in adults aged 50 years or older.

"These results occurred during an influenza season characterized by widespread circulation of antigenically mismatched strains of influenza A/H3N2," the authors say, highlighting that the efficacy results are consistent with those reported from previous trials that showed efficacy and antibody responses against A/H3N2.

These data are reassuring, Dr Orenstein told Medscape Medical News.

"This is a very encouraging study indicating that the recombinant vaccine, consisting of about three times as much hemagglutinin per influenza strain compared to standard inactivated influenza vaccines, may induce higher effectiveness than the standard vaccine in persons 50 years of age or older."

Discussing the superior effectiveness of RIV4 against influenza A, Dr Orenstein emphasized that "absolute differences in laboratory-confirmed influenza infections between the RIV4 and the standard IIV4 were small, in the order of a 1% lower attack rate in the RIV4 group."

Dr Orenstein concluded that although the Advisory Committee on Immunization Practices has not recommended a preference for RIV4 over IIV4, overall, the data from this study "show that RIV4 is a safe and effective alternative to IIV4."

This study was supported by a contract with Protein Sciences from the Biomedical Advanced Research and Development Authority. Three authors report being employed by, and holding stock in, Protein Sciences. One coauthor reports receiving consulting fees from Altimmune, FluGen, Georgia Institute of Technology, Medicago, VaxInnate, Vaxart, Vivaldi Biosciences, Moderna Therapeutics, Novavax, Seqirus, and Visterra. Another coauthor reports receiving consulting fees from Pfizer, Johnson & Johnson, Novartis, and the Bill and Melinda Gates Foundation. The remaining authors and Dr Orenstein have disclosed no relevant financial relationships.

N Engl J Med. 2017;376:2427-2436. Abstract

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