"The US Food and Drug Administration (FDA) has cleared the cobas Influenza A/B test for use on the cobas Liat System, according to manufacturer Roche.
It is the first Clinical Laboratory Improvement Amendments (CLIA)-waiv"...
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 hemagglutination inhibition (HI) antibody).
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)2. The trial 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. 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 4 for a presentation of VE by case definition and antigenic similarity.
Table 4: 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||1.0||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||49.0||(24.7, 65.9)|
|Type B||23||1.0||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 trial.
4 All culture-confirmed cases are considered, regardless of whether they qualified as CDC-ILI.
5 Secondary endpoint of trial.
6 Exploratory (prespecified) endpoint of trial.
Immunogenicity In Adults 50 years Of Age And Older
Two randomized controlled clinical trials of Flublok in adults aged 50 years and older evaluated immune responses by measuring hemagglutination inhibition (HI) antibody titers to each virus strain in the vaccine in adults as compared to another U.S.-licensed trivalent influenza vaccine (IIV3). In these studies, postvaccination immunogenicity was evaluated on sera obtained 28 days after administration of a single dose of Flublok or comparator vaccine. Hemagglutination inhibition geometric mean titers (GMTs) were determined for each vaccine antigen. Immunogenicity was evaluated by calculating GMT ratios of IIV3 to Flublok.
Study 2 was a randomized, observer-blind, comparator-controlled, multi-center trial in healthy adults 50 through 64 years of age to evaluate the immunogenicity of Flublok as compared to a U.S.-licensed IIV3 (Fluzone).3 Results are presented in Table 5. A total of 602 subjects were enrolled, randomized 1:1, and vaccinated with Flublok (300 subjects) or IIV3 (302 subjects). Of the total vaccinated population, 601 subjects (299 Flublok and 302 IIV3 recipients, respectively) were evaluable for immune response (per protocol population for immunogenicity). Subjects were predominantly white (71%) and female (63%) with a mean age of 55.8 years. Immune response endpoints were HI GMTs for each vaccine antigen at baseline and at 28 days post-vaccination. GMTs were compared based on the upper bound of the twosided 95% confidence interval (CI) of the GMT ratio of IIV3 to Flublok. Success in meeting this endpoint was pre-defined as an upper bound (UB) of the two-sided 95% CI of GMTIIV3 / GMTFlublok ≤ 1.5 5. Flublok met the success criterion for HI GMTs for all three antigens. Sub-population analyses of immunogenicity did not reveal significant differences between genders. Sub-analyses according to race and ethnicity were not informative because the study population was not sufficiently diverse.
Study 3 was a randomized, observer-blind, comparator-controlled, multi-center trial in 869 medically stable elderly adults ≥ 65 years of age to evaluate the immunogenicity of Flublok as compared to a U.S.-licensed IIV3 (Fluzone)4. Subjects were randomized 1:1 to receive Flublok (436 vaccinated; 431 evaluable) or IIV3 (433 vaccinated; 430 evaluable). Subjects were predominantly white (98%) and female (53%) with a mean age of 73 years. Immune responses (HI GMTs and GMT ratios) were evaluated in the same manner as for Study 2. The UB of the two-sided 95% CI for the GMT ratio of IIV3 to Flublok was ≤ 1.5 for all three vaccine antigens. Sub-population analyses of immunogenicity did not reveal significant differences between genders, but were not informative with respect to race or ethnicity because the study population was not sufficiently diverse.
Table 5: Comparison of Pre- and Post-Vaccination
Geometric Mean Titers (GMT) for Flublok and Fluzone, Study 2 (adults 50 through
64 years) and Study 3 (adults ≥ 65 years)1,2
|Study Number||Antigen||Post-vaccination GMT Flublok
|Post-vaccination GMT Fluzone
|GMT Ratio Fluzone/ Flublok [95% CI]|
|Study 2 Age 50-64 years||A/H1N1||181.3||139.7||0.77 (0.75, 0.79)|
|A/H3N2||105.4||60.9||0.58 (0.53, 0.62)|
|B||110.9||116.0||1.05 (1.01, 1.09)|
|Study 3 Age ≥ 65 years||Antigen||Post-vaccination GMT Flublok
|Post-vaccination GMT Fluzone
|GMT Ratio Fluzone/ Flublok [95% CI]|
|A/H1N1||176.8||148.1||0.84 (0.81, 0.86)|
|A/H3N2||338.5||199.2||0.59 (0.57, 0.60)|
|Abbreviations: CI, confidence interval; GMT, geometric
1The pre-defined success criterion for the GMT ratio of Fluzone to Flublok was that the upper bound of the 2-sided 95% CI of the GMT ratio, GMT Fluzone / GMT Flublok at 28 days post-vaccination, must not exceed 1.5.
2 HI titers were assayed using BEVS-derived (non-egg-derived) antigens.
1. Treanor JJ, Schiff GM, Hayden FG, et.al. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA. 2007, Vol. 297, pp. 1577-1582.
2. Treanor JJ, El Sahly HM, King J, et. al. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok) against influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine. 2011, Vol. 29, pp. 7733-7739.
3. Baxter R, Patriarca PA, Ensor K, et al. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine. 2011, Vol. 29, pp. 2272-2278.
4. Keitel WA, Treanor JJ, El Sahly HM, et.al. Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccines (TIVs) among persons ≥ 65 years old. Vaccine. 2009, Vol. 28, pp. 379-385.
5. CBER/FDA. Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines. s.l. : DHHS/CBER/FDA, 2007.
Last reviewed on RxList: 5/7/2015
This monograph has been modified to include the generic and brand name in many instances.
Additional Flublok Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.