High-dose Influenza Vax Reduces Respiratory Illness in Nursing Home Residents

September 14, 2017

The quadrupled antigen in a high-dose influenza vaccine did reduce morbidity and mortality, but flaws in the recent study prompt questions.

[[{"type":"media","view_mode":"media_crop","fid":"63238","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3666674588460","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8070","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 281px; width: 325px; float: right;","title":" ","typeof":"foaf:Image"}}]]Medicare could save a ton of money if it could hire a lawyer to take the flu viruses to court to sue them for the age discrimination in death rates. Influenza causes tens of thousands of deaths and hundreds of thousands of hospitalizations annually with the over-65 age cohort being hit the hardest; 80% of all deaths are in this age group. Paradoxically, this age group has the highest flu vaccination rate, but the aging immune system just doesn’t respond as well to the standard flu vaccine compared to younger vaccine recipients. Because of this, researchers have been trying to improve the flu vaccine given to the elderly.

Sanofi was the first to develop a flu vaccine specifically for those over 65 years of age. Their Fluzone High-Dose is made by quadrupling the amount of antigen found in the standard flu vaccine. Testing prior to licensure showed significantly higher antibody levels in persons receiving the high-dose vaccine as compared to the standard dose. But higher antibody levels do not always mean better protection. For example, an 11-year-old produces a much higher antibody response to the HPV antigens in Gardasil than a 16-year-old, but efficacy is the same in preventing infection in both groups.

So, what is the clinical efficacy of this high-dose vaccine? As the saying goes, the proof is in the pudding.

A Sanofi-sponsored study published in the Lancet Respiratory Medicine in July 2017 recruited 823 nursing homes with more than 38,000 subjects with a mean age of 84 years. The nursing homes were randomized to receive either the standard dose or the high-dose Sanofi influenza vaccine for its patients during the 2013-2014 influenza season. Vaccination rate was ~77%. Recipients in the nursing homes assigned to the high-dose group had 12.7% fewer hospitalizations for respiratory illness and an 8% reduction in the rate of all-cause hospitalization. Unfortunately, no lab data looking for actual influenza infection were obtained. The authors estimated that vaccination of 69 persons would translate to one fewer hospitalization of any cause.

The authors estimated that vaccination of 69 persons would translate to one fewer hospitalization of any cause.

An accompanying editorial felt this reduction was “unexpectedly large” and could only be achieved if vaccination also reduced non-respiratory admissions. No significant difference in all-cause mortality rates was noted. The editorial also points out that study was done in a year when the predominant circulating strain (A(H1N1)pdm09) had a historically smaller impact on hospitalizations among the elderly. Since approval of High-Dose Fluzone, other effective options have become available for the over-age-65 population incluidng an adjuvanted influenza vaccine (Fluad, Seqirus Vaccines Limited, UK) and a recombinant recombinant hemagglutinin vaccine (Flublok, Protein Sciences Corporation, Meriden, CT, USA).

All in all, an intriguing study with some flaws.




Gravenstein S, Davidson HE, Taliaard M, et al.  Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: a cluster-randomised trial. Lancet Resp Med. 2017. Published July 20, 2017.

Widdowson M-A, Bresee JS. High-dose influenza vaccine in nursing home residents: not to be sneezed at [editorial]. Lancet Resp Med. Published July 20, 2017.