From Medscape Medical News
Jim Kling
February 14, 2011 — An H5 influenza vaccine that is antigenically out of date can be effectively used as a primer for a second dose of a contemporary antigen.
The strategy could help public health officials respond quickly to a pandemic, because they could give the first dose immediately, without having to wait for the delivery of a novel vaccine, according to a study published in the March issue of the Journal of Infectious Diseases.
Avian influenza viruses of the H5N1 subtype have caused severe disease in humans, prompting concerns that an H5N1 virus could develop into a pandemic form. Effective immunization would likely require 2 doses, but inactivated H5N1 vaccines have generated low frequencies of immune response, which could pose difficulties for an immunization program.
The United States has stockpiled 20 million doses of A/Vietnam/04 vaccine. The researchers wanted to determine the effect of priming with this older strain on a later dose of the more contemporary H5 antigen (A/Indonesia/05). They also determined the effect of dose timing on induced immunity.
The study included 505 healthy adults aged 18 to 49 years (41% men, 59% women) who received 2 vaccine doses. The participants were divided into various groups, with some given only A/Vietnam/04 vaccine, some only given A/Indonesia/05, and others given a combination of the 2 doses.
For each participant, the researchers determined the geometric mean titer (GMT) of serum hemagglutinating inhibiting (HI) antibody and microneutralizing antibody. Neither group showed any cross-reactivity; that is, if they were vaccinated with A/Vietnam/04, they produced no antibodies to A/Indonesia/05.
When a dose of A/Vietnam/04 vaccine was used to prime a later booster with A/Indonesia/05, participants developed antibodies to both virus types (HI GMT 13.6 to A/Vietnam/04 vaccine and 10.1 to A/Indonesia/05 vaccine at day 56). These levels were lower than the levels achieved when 2 doses of homologous vaccines were given to another group of participants, although it was not statistically significant for A/Vietnam/04 antigen (A/Vietnam/04 antigen HI GMT on day 56, 22.9 vs 13.6 [P = .372]; A/Indonesia/05 vaccine HI GMT on day 56, 27.6 vs 10.1 [P = .001]). Similar trends were seen in the measurement of microneutralizing antibody (P = .05 for each comparison).
A regimen of both antigens combined in half doses also produced responses to both viruses. At days 0 and 28, the researchers observed no significant difference between HI antibody to A/Indonesia/05 antigen after A/Indonesia/05 vaccine alone or after a combination vaccine consisting of 45 μg A/Vietnam/04 vaccine and 45 μg A/Indonesia/05 vaccine.
The researchers found that doses on days 0 and 7 created some immunity. Dosing regimens of days 0 and 14 and 0 and 28 produced a stronger response. The best response came at the longest interval, between 0 and 180 days. In a pandemic, this time period is likely to be too long for effective countermeasures. The authors suggest further research to determine whether the same patterns hold with adjuvanted vaccines.
Inducement of titers high enough to confer protection against novel hemagglutinin antigens will require 2 doses. The immune responses measured in the study were modest, but the results hint at potential strategies for vaccinating against an avian influenza outbreak The results suggest that at-risk individuals could be preimmunized with a dose of antigenically distantly related H5 to conserve new vaccine.
The results echo immunization experience with the 2009 H1 vaccine, when a single dose of 2009 H1 HA subunit vaccine produced a response in persons aged 10 years and older. The authors believe that previous H1 infection had primed them to respond to the vaccine, even though the antigen of the previous infection was probably distantly related.
J Infect Dis. 2011;203:666-673. Abstract
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