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Experts discuss options for flu vaccines
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Additional guidance needed to help providers with influenza vaccine choices
I was disappointed by the recently published recommendations and reports on influenza by the CDC’s Advisory Committee on Immunization Practices. It was an extensive document, but purposefully gave no advice on which vaccines are preferable. The committee’s statement, “No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one product is otherwise appropriate,” begs the question of what is advisable based on available information.
Trivalent vs. quadrivalent vaccines
The first question relates to trivalent vs. quadrivalent influenza vaccines. Of course, there are price differences between the two types of vaccines, but price aside, the question of superiority seems to be a no-brainer. Other than price, there is no down side to the quadrivalent vaccines, but there is an upside of more protection against influenza. Given that influenza caused by B strains is much less important in adults than that caused by A strains, there can be no argument that prevention of cases caused by B strains is advantageous. In fact, influenza B can cause serious — and, in fact, fatal — disease in adults; albeit rarely, as evidenced in a study by Paddock and colleagues in a 2012 study.
There are two main antigenic lineages of influenza B virus: Victoria and Yamagata. Antibody against one does not protect against the other. During the 10 seasons from 2001-2002 to 2010–2011, the predominant circulating influenza B virus lineage was represented in the trivalent vaccine in only five seasons — no better than a coin flip. Both influenza B virus antigenic lineages (Victoria and Yamagata) are included in the quadrivalent vaccines, whereas the trivalent vaccines only include the Yamagata lineage. If influenza B antigen is worth including in the vaccine for adults, it might as well be the right one.
Donald Kaye
The other unanswered question relates to which vaccine to use in the elderly. Again, I feel that price aside, it is a no-brainer to use the high-antigen vaccine in the elderly. It is widely known that the elderly population does not respond as well with antibody titers as the younger population and that response is increased to the high-antigen vaccine. To be fair, important data have become available recently, probably after the recommendations of the committee were prepared, that seems to be convincing, if confirmed.
On Aug. 26, Sanofi-Pasteur announced preliminary results of a large-scale, multicenter efficacy trial in adults aged at least 65 years showing a superior clinical benefit of Fluzone High-Dose influenza vaccine relative to the standard dose of Fluzone influenza vaccine in preventing influenza infection. In the study, Fluzone High-Dose vaccine was 24.2% more effective in preventing influenza in adults aged at least 65 years than Fluzone vaccine.
The study results suggested consistent clinical benefit across the study years, influenza virus types, clinical illness definitions and laboratory methods of influenza confirmation. Clearly, the results have to be published in full, but the outcome seems to favor the high-antigen vaccine.
No data are available comparing clinical outcomes in the elderly given trivalent high-antigen vaccine vs. quadrivalent influenza vaccine, but the data that are available favor the high-antigen vaccine in the elderly, as influenza A (H3N2) is a much larger problem for the elderly than influenza B viruses. A quadrivalent high-antigen vaccine might be nice, but none exists.
Choice of vaccines
Well, I plan to receive my high-antigen trivalent vaccine in mid- to late October. Why didn’t I pay attention to all of the warnings to get it as early as possible? There have been a number of studies indicating that the elderly lose antibody more rapidly with time than a younger population.
Furthermore, a case-control study conducted in Spain by Castilla and colleagues during the 2011-2012 influenza season revealed a decline in vaccine effectiveness from 61% in the first 100 days after vaccination, to 42% for days 110 to 119 to virtually no effectiveness thereafter. This decline primarily affected patients aged at least 65 years.
Given that the vaccine strains were not well matched to the circulating strains the year of the study, I do believe that for folks my age, immunity lasts for a shorter period than in younger people. I feel it is best for the elderly to wait at least until mid-October for their immunization for seasonal influenza. The influenza season rarely occurs before mid-December and can occur as late as the end of March. It is a balancing game with present information about whether to risk missing a very early season vs. losing immunity too soon for a late season. The Sanofi-Pasteur study may give us the data we need to better define the duration of immunity with the high-antigen vaccine.
References:
CDC. MMWR. 2013;62(RR-07):1-43.
Paddock CD. J Infect Dis. 2012;205:895-905.
Sanofi-Pasteur. Sanofi Pasteur’s Fluzone High-Dose vaccine significantly more effective than standard dose Fluzone vaccine in preventing influenza in adults 65 years of age and older. Aug. 26, 2013.
For more information:
Disclosure: Kaye reports no relevant financial disclosures.
Influenza vaccine choices: Another view
I certainly agree with my colleague Donald Kaye, MD, that some guidance would be helpful, especially in view of the fact that six new influenza vaccines have been released in the past 18 months. The lack of preferential statements in Advisory Committee on Immunization Practice’s documents such as this has been standard practice ever since ACIP began issuing recommendations.
In the 1970s, this absence prompted Gene H. Stollerman, MD, MACP, then a Regent of the American College of Physicians (ACP), to convince the College that it should play a role here and provide specific recommendations to internists. A working committee was formed, and for more than a decade, several editions of a booklet, titled “Guide to Adult Immunization,” were published by the College. This succeeded in providing recommendations, but failed on the issue of timeliness. There is a residual working group on vaccines within the ACP, and some advice from it would be helpful.
Theodore C.
Eickhoff
The Infectious Diseases Society of America had a Vaccines Committee 30 to 40 years ago, but it seems to have passed out of existence. It hasn’t been heard from in decades.
Lacking recommendations from CDC, ACP and IDSA, where can one turn for guidance? A trusted colleague is the most frequent choice; hopefully, one who knows something about vaccines. Columns in Infectious Disease News might also be helpful; at least that would be timelier than more official sources.
Among the trivalent inactivated influenza vaccines available is a vaccine for intradermal use, from Sanofi-Pasteur. There have been ardent and vocal supporters of intradermal influenza vaccine since 1957. I have never been convinced of its role except, perhaps, when trying to conserve antigen for one or another reason. This vaccine contains only 9 mcg of each antigen, in contrast to the 15 mcg per antigen in standard trivalent vaccines.
Furthermore, there is plenty of antigen available today. One might consider using it only in patients previously immunized multiple times, thus using it only as an annual “booster.” I can’t think of any circumstance when I would recommend it today.
One problem with intradermal vaccines has been that, unless the vaccinator was experienced in intradermal injections, the vaccine often was delivered subdermally. The immunogenicity kinetics were then likely more comparable to subcutaneous injection. Hopefully, the microinjection system sold with intradermal vaccine obviates this problem.
Contrasting points of view
Finally, I disagree with Dr. Kaye on one issue: the addition of 60 mcg of a second B antigen to the high-dose trivalent vaccine for those aged 65 years and older. Quadrivalent vaccines were developed largely and perhaps solely for pediatricians; influenza B of either lineage is a significant cause of morbidity and mortality in pediatrics. There is much less risk to adults and little, if any, in the elderly.
Influenza B does not cause excess mortality and causes only little workplace absenteeism in adults. The immunogenicity of the B component in the elderly was no better than the standard 15 mcg dose; this was in sharp contrast to the two influenza A components. One can search high and low for evidence of clinical efficacy of the B vaccine component in elderly populations, and find very little even when there is a good match. In fact, I’d be quite willing to remove the B component from the high-dose vaccine altogether.
For more information:
Disclosure: Eickhoff reports no relevant financial disclosures.