Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older : RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness among older adults.

Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older:

MEDIA IN THIS ARTICLE

FIGURE 1Screening, Enrollment, and Follow-up.

FIGURE 2Confirmed Cases of Influenza-like Illness.

Lisa M. Dunkle, M.D., Ruvim Izikson, M.D., M.P.H., Peter Patriarca, M.D., Karen L. Goldenthal, M.D., Derek Muse, M.D., Janice Callahan, Ph.D., and Manon M.J. Cox, Ph.D., for the PSC12 Study Team^*

N Engl J Med 2017; 376:2427-2436June 22, 2017DOI: 10.1056/NEJMoa1608862

BACKGROUND

Improved influenza vaccines are needed to control seasonal epidemics. This trial compared the protective efficacy in older adults of a quadrivalent, recombinant influenza vaccine (RIV4) with a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) during the A/H3N2-predominant 2014–2015 influenza season, when antigenic mismatch between circulating and vaccine influenza strains resulted in the reduced effectiveness of many licensed vaccines.

METHODS

We conducted a randomized, double-blind, multicenter trial of RIV4 (45 μg of recombinant hemagglutinin [HA] per strain, 180 μg of protein per dose) versus standard-dose IIV4 (15 μg of HA per strain, 60 μg of protein per dose) to compare the relative vaccine efficacy against reverse-transcriptase polymerase-chain-reaction (RT-PCR)–confirmed, protocol-defined, influenza-like illness caused by any influenza strain starting 14 days or more after vaccination in adults who were 50 years of age or older. The diagnosis of influenza infection was confirmed by means of RT-PCR assay and culture of nasopharyngeal swabs obtained from participants with symptoms of an influenza-like illness. The primary end point was RT-PCR–confirmed, protocol defined, influenza-like illness between 14 days or more after vaccination and the end of the influenza season.

RESULTS

A total of 9003 participants were enrolled and underwent randomization; 8855 (98.4%) received a trial vaccine and underwent an efficacy follow-up (the modified intention-to-treat population), and 8604 (95.6%) completed the per-protocol follow-up (the modified per-protocol population). Among RIV4 recipients, the RT-PCR–confirmed influenza attack rate was 2.2% (96 cases among 4303 participants) in the modified per-protocol population and 2.2% (96 cases among 4427 participants) in the modified intention-to-treat population. Among IIV4 recipients, the attack rate was 3.2% (138 cases among 4301 participants) in the modified per-protocol population and 3.1% (138 cases among 4428 participants) in the modified intention-to-treat population. A total of 181 cases of influenza A/H3N2, 47 cases of influenza B, and 6 cases of nonsubtypeable influenza A were detected. The probability of influenza-like illness was 30% lower with RIV4 than with IIV4 (95% confidence interval, 10 to 47; P=0.006) and satisfied prespecified criteria for the primary noninferiority analysis and an exploratory superiority analysis of RIV4 over IIV4. The safety profiles of the vaccines were similar.

CONCLUSIONS

RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness among older adults. (Funded by Protein Sciences; ClinicalTrials.gov number, NCT02285998.)

Supported by a contract (HSSO 100200900106C) with Protein Sciences from the Biomedical Advanced Research and Development Authority.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. Dunkle, Izikson, and Cox report being employed by and holding stock in Protein Sciences; Dr. Patriarca, receiving consulting fees from Altimmune, FluGen, Georgia Institute of Technology, Medicago, VaxInnate, Vaxart, Vivaldi Biosciences, Moderna Therapeutics, Novavax, Seqirus, and Visterra; and Dr. Goldenthal, receiving consulting fees from Pfizer, Johnson & Johnson, Novartis, and the Bill and Melinda Gates Foundation. No other potential conflict of interest relevant to this article was reported.

SOURCE INFORMATION

From Protein Sciences, Meriden, CT (L.M.D., R.I., M.M.J.C.); Biologics Consulting, Rockville, MD (P.P.); independent consultant, San Antonio, TX (K.L.G.); Jean Brown Research, Salt Lake City (D.M.); and Callahan Associates, San Diego, CA (J.C.).

Address reprint requests to Dr. Dunkle at Protein Sciences, 1000 Research Pkwy., Meriden, CT 06450, or at ldunkle@proteinsciences.com.

A complete list of the members of the PSC12 Study Team is provided in theSupplementary Appendix, available at NEJM.org.

from ! Medicine by Alexandros G. Sfakianakis via alwin on Inoreader http://ift.tt/2sx8vrL
via IFTTT