The 2012 recommendations from the CDC Advisory Committee on Immunization Practices for the prevention and control of seasonal influenza with vaccines recommended universal vaccination of all individuals over the age of 6 months who do not have contraindications and discussed options regarding specific vaccines (1).
The 2010 recommendations from the CDC Advisory Committee on Immunization Practices for the prevention and control of seasonal influenza with vaccines identified high-risk populations who should be targeted for vaccination or who should preferentially receive vaccine in times of shortage (2).
A 2012 systematic review of the effect of influenza vaccination on confirmed cases of influenza included a total of 17 randomized trials and 14 observational trials. TIV had a pooled efficacy of 59% (CI, 51% to 67%) in adults aged 18 to 65; no trials of children or the elderly met inclusion criteria. LAIV had a pooled efficacy of 83% (CI, 69% to 91%) in children aged 6 months to 7 years. Pandemic H1N1 vaccine had an efficacy of 69% (CI, 60% to 93%) (3).
A 2010 Cochrane review of influenza vaccination in healthy adults included 50 reports. During seasons when vaccine strains match circulating strains, vaccination lowered rates of symptomatic influenza from 4% to 1% of the population; when strains do not match, vaccination lowered rates of symptomatic influenza from 2% to 1% (4).
A 2010 Cochrane review of the efficacy of influenza vaccination in the elderly included 75 studies, of which only one was a randomized trial. Evidence was of poor quality but appeared to show that vaccination decreased symptoms of influenza (5).
A 2011 systematic review addressed the effectiveness of the inactivated influenza vaccine in preventing laboratory-confirmed influenza among healthy adults (16 to 65 years) and children (6 years or older). The review found that vaccine was generally effective but was limited by little good-quality evidence of the effectiveness of influenza vaccination on complications such as pneumonia, hospitalization, and influenza-specific and overall mortality, and in certain groups such as children under 6 years, individuals with chronic obstructive pulmonary disease, institutionalized elderly (65 years or older), elderly with comorbidities, and health care workers in homes for the elderly (6).
A 2012 systematic review of the effect of influenza vaccination in immunocompromised patients included 209 studies. There were 13 studies of patients with HIV, of which 2 were appropriate for inclusion in the meta-analysis. Despite heterogeneity, those studied showed that vaccination reduced influenza-like illness (pooled OR, 0.20 [CI, 0.05 to 0.88]). Studies in HIV patients found few significant adverse effects. Similarly, influenza vaccination reduced influenza-like illness in patients with cancer (pooled OR, 0.26 [CI, 0.15 to 0.46]) and in patients with transplants (pooled OR, 0.27 [CI, 0.11 to 0.66]), with few adverse effects (7).
A 2012 Cochrane review of influenza vaccination in healthy children included 17 randomized, controlled trials, 19 cohort studies, and 11 case-control studies. Overall, influenza vaccination prevented cases of influenza in children 2 years or older, with an NNT of 6 for children under age 6 and an NNT of 28 for those over age 6. There was little evidence for children under age 2. There was no evidence of effect of the vaccine on secondary cases, lower respiratory tract disease, drug prescriptions, otitis media and its consequences, and socioeconomic impact (8).
A 2010 Cochrane review of the effect of health care worker vaccination on rates of influenza in long-term care facilities included 4 randomized trials and 1 cohort study. Health care worker vaccination did not affect rates of confirmed influenza (OR, 0.87 [CI 0.38 to 1.99]), pneumonia (OR, 0.71 [CI 0.29 to 1.71]), or death from pneumonia (OR, 0.87 [CI 0.47 to 1.64]), although it did reduce influenza-like illness (RR, 0.71 [CI 0.58 to 0.88]) (9).
A 2009 Cochrane review of one randomized, controlled trial of influenza vaccination in children receiving chemotherapy for cancer included eight trials. Immune responses in children receiving chemotherapy were consistently weaker (four-fold rise of 25% to 52%) than in children who had completed chemotherapy (50% to 86%) and in healthy children (71% to 89%) (10).
A randomized, controlled trial including a total of 1340 healthy subjects aged 18 years and older showed that a single dose of the 3.75-mcg hemagglutinin AS03(A)-adjuvanted H1N1 2009 influenza vaccine induced the strongest immune responses in subjects aged 18 to 64 years, as well as in subjects over age 64, compared with 1.9-mcg hemagglutinin AS03(B) or nonadjuvanted vaccine formulation (11).
A prospective, randomized, open, blinded end-point study enrolled 439 patients who had been admitted due to acute coronary syndrome within 8 weeks and randomly assigned to receive either TIV or no treatment. The study showed that TIV was associated with reduction of major cardiovascular events, including death, hospitalization from acute coronary syndrome, hospitalization from heart failure, and hospitalization from stroke (12).
In a randomized trial, healthy adults aged 18 to 44 years, 45 to 64 years, and 65 years and older received two doses of pandemic H1N1 vaccine given 21 days apart: either 7.5 mcg of hemagglutinin formulated as whole-virion vaccine or 3.75 mcg of hemagglutinin formulated as split-virion vaccine with AS03(A) oil-in-water adjuvant. The study showed that AS03(A)-adjuvanted vaccine was more immunogenic against pandemic influenza A H1N1 virus than whole-virion vaccine. The immunogenic response was better with two doses of the vaccine than one in older adults (13).
A randomized, controlled trial among 117 participants aged 22 to 62 years showed that previous vaccination with the seasonal trivalent influenza vaccine was associated with a weak antibody response to the pandemic H1N1 2009 vaccine. The authors recommended that the pandemic H1N1 2009 vaccine be administered before vaccination with the seasonal trivalent influenza vaccine (14).
A multicenter clinical trial to evaluate the immunogenicity and safety of H1N1 vaccine in young adults (18 to 64 years) and the elderly (65 years or older) using a two-dose regimen, with the doses administered 21 days apart, showed that the increase in hemagglutination inhibition titers was higher with MF59-adjuvanted vaccine than with nonadjuvanted vaccine. In the elderly, on day 21 after the first dose, the rates of seroprotection and seroconversion were significantly higher for the 7.5-mcg dose of MF59-adjuvanted vaccine than for the 3.75-mcg dose (58.0% versus 44.3% [P=0.03] and 53.7% versus 37.2% [P<0.01], respectively) (15).
A randomized, blinded, controlled trial among 261 healthy adults aged 18 to 60 years showed that AS03(A)-adjuvanted H1N1 vaccine containing 3.75 mcg was more immunogenic than nonadjuvanted H1N1 vaccine containing 15 or 3.75 mcg of hemagglutinin (16).
A randomized trial including 150 HIV patients aged 20 to 59 years demonstrated that a single dose of a single-antigen, inactivated, split, AS03(A)-adjuvanted H1N1 influenza vaccine induced high-level immunogenicity. Seroprotection and seroconversion were further improved in those patients randomly assigned to booster dosing at day 21 compared with a single-dose vaccination (17).
A randomized trial compared TIV with placebo in 506 HIV-infected adults in South Africa. The efficacy of TIV against confirmed influenza illness was 75.5%. Seroconversion, measured by hemagglutination inhibition titers, was evident in 52.6% for H1N1, 60.8% for H3N2, and 53.6% for influenza B virus (18).
A randomized, controlled trial included 340 pregnant women in Bangladesh who received either inactivated influenza vaccine or 23-valent pneumococcal polysaccharide vaccine (control). During the period with circulating influenza virus, there was a substantial reduction in the incidence per 100 person-months of respiratory illness with fever among the mothers and infants who had received the influenza vaccine (influenza vaccine: 3.7; control: 7.2; P=0.0003). Furthermore, the proportion of infants who were small for gestational age was lower in the influenza vaccine group than in the control group (25.9% vs. 44.8%; P=0.03) (19).
A randomized trial enrolled 120 pregnant women who received an inactivated 2009 H1N1 influenza vaccine containing either 25 mcg or 49 mcg of hemagglutinin in a two-dose series with a 21-day period between administration of the first and second doses. The study showed that one dose of an inactivated 2009 H1N1 influenza vaccine containing 25 mcg of hemagglutinin elicited an antibody response (hemagglutination inhibition titers of ≥1:40) typically associated with protection against influenza infection in both the mother and the cord blood (20).
A randomized trial compared influenza vaccination to pneumococcal vaccination in 340 pregnant women. There were fewer cases of documented influenza in the infants of vaccinated mothers compared with infants of unvaccinated women, with an effectiveness of 63% (CI, 5% to 85%) (21).
A prospective, multicenter trial demonstrated the immunogenicity and reactogenicity of two doses of AS03(B)-adjuvanted pandemic influenza vaccine in 302 children aged 6 months to 12 years (22).
A randomized, double-blind, active-controlled, phase III study confirmed a new trivalent inactivated split-virus influenza vaccine to be immunogenic and safe in 283 healthy children aged 6 months to less than 18 years (23).
A randomized, observer-blinded, multicenter trial in 474 children aged 6 to 35 months or 3 to 9 years confirmed the immunogenicity and safety of two doses of a monovalent inactivated pandemic (H1N1) 2009 vaccine containing 7.5 or 15 mcg of hemagglutinin. The first dose of either H1N1 vaccine formulation was more immunogenic in children over 3 years than in younger children (24).
An immunization registry showed that one dose of 2009 influenza A (H1N1) vaccine was effective in preventing hospitalization due to pandemic H1N1 influenza in children aged 7 months to 9 years (25).
In a multicenter, randomized, head-to-head trial, vaccination with two doses of an AS03(B)-adjuvanted split-virion H1N1 influenza vaccine was more effective in inducing protective antibodies than a nonadjuvanted whole-virion H1N1 influenza vaccine among 318 children. A single dose of trivalent seasonal influenza vaccine was found to be immunoprotective among 302 children (26).
A randomized, controlled trial confirmed that two age-appropriate doses of TIV with the MF59 adjuvant was more effective than TIV without the MF59 adjuvant against PCR-confirmed influenza in 4707 healthy children aged 6 months to under 72 months who had not previously been vaccinated against influenza (27).
A randomized, open-label trial among 392 children showed similar immunogenicity of one dose of nonadjuvanted A/H1N1 vaccine, one dose of MF59-adjuvanted vaccine, or two doses of nonadjuvanted vaccine in 9- to 17-year-olds. However, in children aged 3 to 8 years, only one dose of the adjuvanted vaccine or two doses of nonadjuvanted vaccine achieved protective titers (28).
A randomized, controlled trial showed that the 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic, safe, and well tolerated in 36 HIV-infected children and adolescents as in 36 age- and gender-matched healthy controls (29).
A prospective study of 199 patients with autoimmune diseases confirmed the safety and efficacy of seasonal TIV and A/H1N1 influenza vaccines where 80% and 65% of study subjects achieved seroprotection, respectively (30).
In a randomized, controlled trial that included 81 young patients with type 1 diabetes, one dose of MF59-adjuvanted influenza A(H1N1) vaccine, simultaneously with a single dose of a virosome-adjuvanted TIV was as seroprotective and safe as two doses of the same vaccines (31).
In an open, prospective trial, two doses, not one dose, of the 2009 AS03-adjuvanted influenza H1N1 vaccine in allogeneic, hematopoietic stem-cell transplant recipients elicited comparable responses to a single dose in healthy individuals. Transplant-to-vaccination interval and active graft-versus-host disease were the most powerful predictors of poor antibody responses to vaccine (32).
A randomized, controlled trial comparing the immunogenicity of the TIV seasonal 2008-2009 influenza vaccine containing either 6 mcg (intradermal) or 15 mcg (intramuscular) of hemagglutinin per viral strain in 85 lung-transplant recipients showed poor response (14.6% vs. 18.6% in the intradermal and the intramuscular group, respectively; P=0.77) (33).
A randomized, controlled trial that included 38 breast cancer patients on chemotherapy and 21 healthy controls showed that patients on chemotherapy had significantly lower responses to TIV compared with healthy controls. Vaccination early during the chemotherapy cycle induced better responses than did vaccination at day 16 of the cycle (34).
In a randomized, controlled trial, the immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines was lower in pediatric kidney-transplant recipients than in healthy controls. Furthermore, the simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens (35).
A controlled trial that included 555 patients with systemic lupus erythematosus and 170 healthy controls showed pandemic influenza A H1N1/2009 vaccine response was diminished in SLE under immunosuppressive therapy (such as prednisone >20 mg and other drugs), and antimalarials (chloroquine) seemed to restore this immunogenicity (36).