Laird Harrison

March 11, 2014

SAN DIEGO — People with atopic dermatitis and Staphylococcus aureus colonization have weakened immune responses to the Fluzone intradermal influenza virus vaccine (Sanofi Pasteur), a new study shows.

However, "there is no significant difference between atopic dermatitis and nonatopic dermatitis," said Donald Leung, MD, head of the division of pediatric allergy and immunology at National Jewish Health in Denver.

Dr. Leung presented the study results here at the American Academy of Allergy, Asthma & Immunology 2014.

These findings could have implications not only for this vaccine, but also for other intradermal vaccines, including many under development.

The intradermal vaccine became available in the 2011 flu season. It releases only 0.1 mL of product, compared with the 0.5 mL of the typical vaccine, which allows the same amount of antigen to be distributed to more people. It also features a 1.5 mm needle, making it less painful.

In phase 3 trials, the intradermal injection appeared to be as effective in conferring immunity as intramuscular administration. However, the researchers did not look at atopic dermatitis in those trials, Dr. Leung pointed out.

People with atopic dermatitis are often colonized with S aureus, but the colonizations don't necessarily cause symptoms.

If you bypass the skin, then you had a normal response to Fluzone.

Dr. Leung and his team compared hemagglutination-inhibition antibody titers in subjects 28 days after the administration of the 2012 Fluzone intradermal vaccination. They defined seroprotection as an antibody titer of at least 1:40, and seroconversion as at least a 4-fold increase in titer.

Of the patients with moderate to severe atopic dermatitis, 100 received intradermal vaccine and 102 received intramuscular vaccine. Of the subjects with mild atopic dermatitis, 21 received intradermal vaccine and 23 received intramuscular vaccine. The control group consisted of 111 subjects with no atopy.

In patients with atopic dermatitis, rates of seroprotection and seroconversion were similar for intradermal and intramuscular vaccination.

In the intramuscular group, rates of seroprotection and seroconversion were similar in patients with atopic dermatitis who were colonized with S aureus and those who were not. "If you bypass the skin, then you had a normal response to Fluzone," Dr. Leung explained.

After intradermal immunization for the H3N2 influenza virus, there was little difference in seroprotection and seroconversion in patients with and patients without S aureus. However, after intradermal immunization for the B virus, there was a significant difference in seroprotection and seroconversion, and after intradermal immunization for the H1N1 virus, there was a significant difference seroconversion.

"Among atopic dermatitis subjects, the subset with S aureus colonization exhibited reduced cutaneous immune responses to intradermal vaccination," Dr. Leung reported.

He noted that the researchers only vaccinated through nonlesioned skin.

Table. Intradermal Immunization of Patients With Atopic Dermatitis

Outcome S aureus Colonization, % No S aureus Colonization, % P Value
Influenza B virus      
   Seroprotection 12 47 .001
   Seroconversion 21 51 .002
H1N1 virus      
   Seroprotection 77 93 .082
   Seroconversion 77 95 .029


Next, the team will try to determine why S aureus seems to produce a reduced immune response. In particular, they will try to remove the S aureus to see how that affects the immune response.

"The cynic might say it's not S aureus, it's just a biomarker for a poor immune response," he said.

Such findings could affect the development of other intradermal vaccines, said session moderator Lisa Beck, MD, professor of dermatology at the University of Rochester in New York.

The US Army still uses scarification to vaccinate against small pox, she told Medscape Medical News, and yellow fever vaccines are also sometimes administered this way.

In addition, researchers are trying to develop skin patches to administer vaccine, because disposing of needles is a problem in developing countries, she said.

However, if having S aureus on your skin changes immune response, "it might alter some of the enthusiasm about going through the skin," she said. "Five percent of healthy people have that now. We're talking about not infected skin, but people whom you just swab."

Dr. Beck noted that "it's too early for clinicians to change their recommendations to patients."

This study was funded by the National Institute of Allergy and Infectious Diseases. Dr. Leung disclosed that he has financial relationships with Regeneron and Novartis. Dr. Beck disclosed that she has relationships with Genentech, Janssen and Unilever

American Academy of Allergy, Asthma & Immunology (AAAAI) 2014: Abstract 254. Presented March 1, 2014.


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