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High-Dose Flu Vaccine Boosts Immunity Safely in the Elderly

Posted Oct 26 2008 1:32pm
Increasing the dose of a standard influenza vaccine raised immune responses safely in individuals 65 and older and should improve protection against flu outbreaks, researchers reported.
Action Points  
  • Explain to patients that standard flu vaccines may not offer sufficient protection to older patients, who are at greater risk of complications, and in whom immune competence tends to decrease.
  • Recognize that in this dose-response study higher doses of vaccine boosted immunity safely compared with the standard 15µg dose.

Although the recommended doses of influenza vaccines produce significant responses in most susceptible younger adults, immune competence appears to decrease with increasing age. One way to improve immunogenicity in inactivated vaccines is to increase the dose of antigen in the current U.S. vaccine, researchers wrote in the May 22 Archives of Internal Medicine.

 

At present, recommended vaccines contain 15µg of inactivated virus per strain, said Wendy Keitel, M.D., at Baylor College of Medicine here, and colleagues.

 

In a dose-response study of 202 ambulatory individuals ages 65 and older (mean age 72.4.), participants (41% women) were randomly assigned to a placebo or a single intramuscular injection of a flu vaccine in one of three formulations: 15µg, 30 µg, or 60 µg of hemagglutinin per strain (up to 180 µg total per dose).

 

The vaccine used in the study matched the licensed 2001-2002 formulation of the trivalent inactivated vaccine and was supplied by Aventis Pasteur in a dose range feasible for production.

 

There were no significant differences in baseline characteristics or the percentage of individuals with a pre-immunization titer of at least 32, the researchers reported. Of the participants, 82% reported receiving a flu shot during the preceding flu season, and 18% reported an influenza-like illness during the previous winter.

 

According to clinical and serologic responses assessed during the month after immunization, higher vaccine doses produced significantly higher serum antibody titers, the researchers reported.

 

Mean serum hemagglutination inhibition antibody titers one month after immunization in groups given 0-, 15-, 30-, and 60-µg doses were 23, 37, 50, and 61 against influenza A/H1N1; 43, 86, 91, and 125 against A/H3N2; and 10, 14, 18, and 24 against influenza B, respectively.

 

Compared with participants given the standard 15µg dosage, mean serum hemagglutination inhibition and neutralizing antibody levels against the three vaccine antigens in participants given the 60µg doses were higher by 44% to 71% and 54% to 79%, respectively.

 

Furthermore, the 60µg dosage nearly doubled the frequency of antibody response in those whose pre-immunization antibody titers were in the lower half of the antibody range, the researchers said.

 

Dose-related increases in injection-site reactions—discomfort, redness, swelling—were observed ( P <.001) and were more common among these receiving the 60µg dose compared with the 15µg dose. However, most site reactions were mild, no significant differences among groups were observed for systemic symptoms, and all doses were well tolerated, the researchers reported.

 

This study focused on the current population of elderly individuals, a target group at high risk of influenza complications, hospitalization, and death, and with the greatest need for more effective vaccines, Dr. Keitel said.

 

However, several limitations of this study still need to be addressed in expanded studies, Dr. Keitel said. The sample size was small, and only healthy individuals were recruited. Responses in less vigorous elderly persons may differ, she said.

 

Participants also received the vaccine formulations contained in the previous year's vaccine, and they were immunized less than a year after receiving their most recent vaccine. The effectiveness of advanced-potency vaccines needs to be studied among large group of individuals given the most up-to-date formulations, the researchers pointed out.

 

"Our findings provide a rationale for further, expanded trials designed to assess the effectiveness of immunization with enhanced-potency vaccines in the elderly population," Dr. Keitel concluded.

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