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Influenza Vaccination in Older Populations: Adjuvanted vs Non-Adjuvanted Vaccine Comparisons

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

MEDI-NEWS - Based on Van Buynder et al. Vaccine Published ahead of print August 6, 2013; Scheifele et al. Human Vaccines & Immunotherapeutics 2013;9:11:1-14.

November 2013

Immunosenescence that occurs as a result of normal aging impairs response to any vaccine including influenza vaccines. By adding an adjuvant, an adjuvanted trivalent inactive influenza vaccine (aTIV) has the potential to invoke more robust immune response in vulnerable patient groups compared to non-adjuvanted vaccines, and offers superior protection against influenza illness. In separate studies, the aTIV vaccine proved to be superior to comparator vaccines in terms of its ability to enhance immune response to tested influenza strains. Findings also indicate that enhanced immune response are highly protective against influenza-related hospitalizations in the elderly, among whom hospitalization is often a life-changing event. Even modest improvements in vaccine efficacy can be expected to significantly reduce influenza-related sequelae to which the elderly are disproportionately vulnerable.  

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

An adjuvanted trivalent inactivated influenza vaccine (aTIV) has been shown to be more effective against influenza infection in 2 separate direct comparisons of newer influenza vaccines in older patient populations, according to recent findings.

As such, it suggests older adults will be better protected against influenza infection and its sequelae than is possible with currently available alternative vaccines. “We know that the elderly are disproportionately affected by influenza,” Dr. Paul Van Buynder, Vice President, Population Health and Chief Medical Health Officer, Fraser Health Authority, Vancouver, BC said in an interview. Compared to younger individuals, the elderly are more likely to have severe illness, he continued.

They are also more likely to require hospitalization for influenza illness and die from it. Many elderly who develop influenza lose their ability to remain self-sufficient because of the need for hospitalization and will require discharge to a long-term nursing home facility. During influenza infection, older patients can lose up to 5% of their muscle power and 1% of their aerobic capacity per day of bed rest. “Sadly,” Dr. Van Buynder added, “white blood cells that might otherwise help protect older individuals against influenza illness become less functional with aging—a process known as immunosenescence—and patients are less likely to be protected after receiving routine inactivated vaccines.”

Given this, there is clearly a need to find a better vaccine for the elderly. A vaccine consisting of 3 immunizing antigens with an MF59 oil-in-water adjuvant has been in use in Europe for over a decade but has only recently been licensed in Canada. Dr. Van Buynder and colleagues thus used a case-control study design to compare vaccine efficacy of the aTIV vaccine against the trivalent inactivated influenza vaccine (TIV) in a prospective community-based cohort of elderly individuals. Elderly residents over the age of 75 in 2 health authorities in BC as well as all residents living in long-term care facilities were given the aTIV vaccine (Fluad) during the 2011/2012 influenza season.

In a third health authority, residents in long-term care were offered the same adjuvanted aTIV vaccine but all other elderly were offered standard TIV (predominantly Fluviral). A total of 282 subjects were enrolled for the study—84 subjects who developed influenza and 198 controls who did not. As investigators pointed out, 57% of participants who developed influenza during the 2011/2012 season were in long-term care and almost half were 85 years of age and older. Approximately 90% of them also had at least 1 chronic disease. Slightly fewer subjects were actually vaccinated (n=227) but of those who were, 73% received the aTIV while 27% received the TIV.

Vaccine efficacy for the aTIV was 58% overall for this study population (P<0.04) whereas the TIV was ineffective against influenza illness during the 2011/2012 influenza season. The aTIV was also more effective in the community dwelling groups with a vaccine efficacy rate of 72% (P=0.047). Among the vaccinated study population, the relative vaccine efficacy was 63% for the aTIV vaccine. As Dr. Van Buynder pointed out, the 2011/2012 influenza season was a relatively quiet one.

Over the next influenza season (2012/2013), Dr. Van Buynder and colleagues evaluated vaccine efficacy in another 913 older subjects. Sixty percent of these subjects were in long-term care facilities, and of those who had been vaccinated before, over 80% received the aTIV vaccine. Confining their analysis to long-term care residents only, unpublished findings indicate that the aTIV vaccine prevented at least 85% of influenza-related hospitalizations during the 2012/2013 influenza season.  

“We did have very frail groups in our studies but the vaccine efficacy with aTIV was independent of frailty,” Dr. Van Buynder noted. “So the aTIV is a better vaccine and that’s why we give it to all patients in British Columbia over the age of 65.”

Separate Study

In a separate study, Dr. David Scheifele, Director, Vaccine Evaluation Center, and Professor of Pediatrics, University of British Columbia, Vancouver, and colleagues compared the safety, immunogenicity and tolerability of 3 influenza vaccines in older adults. A total of 922, non-frail community-dwelling adults 65 years of age and older were randomized in relatively equal numbers to receive the intradermal influenza vaccine (IDV), the MF59-adjuvanted vaccine (aTIV) or a TIV formulation of equal potency and strain composition as the aTIV vaccine. Participants had a history of receiving the annual flu shot and were specifically selected because of this. 

Three different assays were used to assess immune response to immunization including the hemagglutination inhibition (HAI) assay; the single radial hemolysis assay and the microneutralization assay. Three weeks after receiving the respective vaccinations, seroprotection rates did differ depending on the assay used. The influenza strains against which the vaccine was tested included only  H1N1 and H3N2, as baseline titers against B/Brisbane were very high in each study group, precluding meaningful response. In contrast, there was a difference in favor of the aTIV vaccine for HAI results.

Based on HAI assay results, HAI titers ≥40 were highest among aTIV recipients with an approximately 12% advantage in terms of immunogenic response over both IDV and TIV. IDV and TIV were alike in terms of seroprotection rates and geometric mean titers (GMTs) to both H1N1 and H3N2 antigens. Importantly, following immunization, GMTs were highest after aTIV for A influenza viral strains.

As Dr. Scheifele and colleagues pointed out, severe outcomes in seniors most often occur with A/H3N2 viral infections. Seroprotection rates also did not differ by age group, presence or number of health conditions or any other variable assessed. Rates of injection site redness were highest in the IDV group while injection site pain rates were highest in the aTIV group.

However, as investigators pointed out, almost all vaccine recipients said they were not bothered by injection site reactions. At day 180 post-vaccination, seroprotection rates had declined by approximately 25% and no longer differed significantly among groups. “Raising antibody levels [in  adults over the age of 65] is challenging,” Dr. Scheifele said in an interview. Seroprotective HAI titers of 40 or greater, for example, were established in young military personnel, suggesting that for seniors, antibody titers may well have to be much higher to provide protection against influenza illness.

There is also evidence that cellular immunity may be more important than antibody immunity to ensure protection in vulnerable elderly patients, Dr. Scheifele added. As an unpublished part of the same study, Dr. Scheifele and colleagues evaluated cellular immune response to the 3 vaccines and they will report on these effects in a separate publication.  Still, as Dr. Scheifele noted, the incremental effectiveness of the adjuvanted vaccine over comparator vaccines, though modest, is clinically meaningful.

In an estimation of the health impact and cost-effectiveness of influenza vaccine with enhanced effectiveness in Canada, Fisman et al. (PLoS ONE 6(11): e27420. doi:10.1371/journal.pone.0027420) projected that replacing traditional aTIVs with MF59-adjuvanted vaccines would confer “substantial benefits” to vaccinated and unvaccinated individuals alike and would be “economically attractive” relative to other widely used preventive interventions.

The Fisman et al. study suggested it would be cost-effective to use a somewhat more expensive vaccine like the MF59-adjuvanted vaccine even if the advantage is small. “This is because there is so much morbidity”, Dr. Scheifele said. “So we should be embracing these new vaccines even if they are not spectacularly better than the old ones.”

Summary

Each year an average of 20,000 hospitalizations and between 2000 and 8000 deaths are attributed to influenza and pneumonia in Canada. Vaccination remains the most important way of preventing influenza illness and its sequelae and an adjuvanted vaccine that enhances the immune response and potentially prevents influenza illness in vulnerable adults represents an improvement over TIV vaccines for seniors here and elsewhere.   

 

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