"The U.S. Food and Drug Administration today announced that it has approved Flublok, the first trivalent influenza vaccine made using an insect virus (baculovirus) expression system and recombinant DNA technology. Flublok is approved for the preve"...
Mechanism of Action
Flublok contains recombinant HA proteins of the three strains of influenza virus specified by health authorities for inclusion in the annual seasonal vaccine. These proteins function as antigens which induce a humoral immune response, measured by hemagglutinin inhibition antibody (HAI).
Antibodies against one influenza virus type or subtype confer limited or no protection against another. Furthermore, antibodies to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual replacement of one or more influenza virus strains in each year's influenza vaccine. Therefore, influenza vaccines are standardized to contain the hemagglutinins of influenza virus strains (i.e., typically two type A and one type B), representing the influenza viruses likely to be circulating in the U.S. in the upcoming winter.
Efficacy Against Culture-Confirmed Influenza
The efficacy of Flublok was evaluated in a randomized, observer-blind, placebo-controlled multicenter trial conducted in the U.S. during the 2007-2008 influenza season (Study 1). The study enrolled and vaccinated 4648 healthy adults (mean age 32.5 years) randomized in a 1:1 ratio to receive a single dose of Flublok (n=2344) or saline placebo (n=2304). Among enrolled subjects, 59% were female, 67% were white, 19% African-American, 11% Latino/Hispanic, 2% Asian and < 1% other. The two groups were similar in demographics. Culture-confirmed influenza was assessed by active and passive surveillance for influenza-like illness (ILI) beginning 2 weeks post-vaccination until the end of the influenza season, approximately 7 months post- vaccination. ILI was defined as having at least 2 of 3 symptoms (no specified duration) in the following categories: 1) fever ≥ 100°F; 2) respiratory symptoms (cough, sore throat, runny nose/stuffy nose); or 3) systemic symptoms (myalgias, arthralgias, headache, chills/sweats, tiredness/malaise). For subjects with an episode of ILI, nasal and throat swab samples were collected for viral culture.
The primary efficacy endpoint was Centers for Disease Control-defined influenza-like illness (CDC-ILI) with a positive culture for an influenza virus strain antigenically resembling a strain represented in Flublok. CDC-ILI is defined as fever of ≥ 100°F oral accompanied by cough, sore throat, or both on the same day or on consecutive days (1). Attack rates and vaccine efficacy (VE), defined as the relative reduction in the influenza rate for Flublok relative to placebo, were calculated for the total vaccinated cohort (n=4,648).
The pre-defined success criterion for the primary efficacy analysis was that the lower bound of the 95% confidence interval (CI) of VE should be at least 40%. Vaccine efficacy against antigenically matched culture-confirmed CDC-ILI could not be determined reliably because 96% of the influenza isolates obtained from subjects in Study 1 were not antigenically matched to the strains represented in the vaccine. An exploratory analysis of VE of Flublok against all strains regardless of antigenic match isolated from any subject with an ILI, not necessarily CDC-defined ILI, demonstrated an efficacy estimate of 44.8% (95% CI 24.4, 60.0). See Table 2 for a presentation of VE by case definition and antigenic similarity.
Table 2: Vaccine Efficacy Against Culture-Confirmed
Influenza in Healthy Adults 18-49 Years of Age, Study 1*
|Flublok Vaccine Efficacy1, %||95% Confidence Interval|
|Cases, n||Rate, %||Cases, n||Rate, %|
|Positive culture with a strain represented in the vaccine|
|CDC-ILI, all matched strains2,3||1||0.04||4||0.2||75.4||(-148.0, 99.5)|
|Any ILI, all matched strains4,5||2||0.1||6||0.3||67.2||(-83.2, 96.8)|
|Positive culture with any strain, regardless of match to the vaccine|
|CDC-ILI, all strains2,6||44||1.9||78||3.4||44.6||(18.8, 62.6)|
|Sub-Type A||26||1.1||56||2.4||54.4||(26.1, 72.5)|
|Type B||18||0.8||23||1||23.1||(-49.0, 60.9)|
|Any ILI, all strains4||64||2.7||114||4.9||44.8||(24.4, 60.0)|
|Sub-Type A||41||1.7||79||3.4||49||(24.7, 65.9)|
|Type B||23||1||36||1.6||37.2||(-8.9, 64.5)|
|*In Study 1 (NCT00539981) vaccine efficacy analyses were
conducted on the Total Vaccinated Cohort (all randomized subjects who received
study vaccine according to the treatment actually received and who provided
data). Vaccine efficacy (VE) = 1 minus the ratio of Flublok/placebo infection
1 Determined under the assumption of Poisson event rates, according to Breslow and Day, 1987.
2 Meets CDC influenza-like illness (CDC-ILI) defined as fever of ≥ 100°F oral accompanied by cough and/or sore throat, on the same day or on consecutive days.
3 Primary endpoint of study.
4 All culture-confirmed cases are considered, regardless of whether they qualified as CDC-ILI.
5 Secondary endpoint of study.
6 Exploratory (prespecified) endpoint of study.
Last reviewed on RxList: 11/25/2013
This monograph has been modified to include the generic and brand name in many instances.
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