Prevention and Control of Influenza, Recommendations of the Advisory Committee on Immunization Practices (ACIP)

Nicole M. Smith, PhD; Joseph S. Bresee, MD; David K. Shay, MD; Timothy M. Uyeki, MD; Nancy J. Cox, PhD; Raymond A. Strikas, MD


Morbidity and Mortality Weekly Report. 2006;55(27):1-41. 

In This Article

Comparison of LAIV with Inactivated Influenza Vaccine

Both inactivated influenza vaccine and LAIV are available. Although both types of vaccines are effective, the vaccines differ in several aspects ( Table 2 ).

Both LAIV and inactivated influenza vaccines contain strains of influenza viruses that are antigenically equivalent to the annually recommended strains: one influenza A (H3N2) virus, one A (H1N1) virus, and one B virus. Each year, one or more virus strains might be changed on the basis of global surveillance for influenza viruses and the emergence and spread of new strains. Viruses for both vaccines are grown in eggs. Both vaccines are administered annually to provide optimal protection against influenza virus infection ( Table 2 ).

Inactivated influenza vaccine contains killed viruses, and thus cannot produce signs or symptoms of influenza virus infection. In contrast, LAIV contains live, attenuated viruses and, therefore, has a potential to produce mild signs or symptoms related to influenza virus infection. LAIV is administered intranasally by sprayer, whereas inactivated influenza vaccine is administered intramuscularly by injection. LAIV is more expensive than inactivated influenza vaccine, although the price differential between inactivated vaccine and LAIV has decreased for the 2006-07 season. LAIV is approved only for use among healthy persons aged 5-49 years; inactivated influenza vaccine is approved for use among persons aged ≥6 months, including those who are healthy and those with chronic medical conditions ( Table 2 ).

The effectiveness of inactivated influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient, the degree of similarity between the viruses in the vaccine and those in circulation, and the outcome being measured. Vaccine efficacy and effectiveness studies might have various endpoints, including the prevention of medically attended acute respiratory illness (MAARI), prevention of culture-positive influenza virus illness, prevention of influenza or pneumonia-associated hospitalizations or deaths, seroconversion to vaccine serotypes, or prevention of seroconversion to circulating influenza virus subtypes. High postvaccination hemagglutination inhibition antibody titers develop in the majority of vaccinated children and young adults.[69,70,71] These antibodies are protective against illness caused by strains that are antigenically similar to those strains of the same type or subtype included in the vaccine.[70,71,72,73]

Children. Children aged ≥6 months usually acquire protective levels of anti-influenza antibody against specific influenza virus strains after influenza vaccination,[69,70,74,75,76,77,78,79] although the antibody response among children at high risk for influenza-related complications might be lower than among healthy children.[80,81] A 2-year randomized study of children aged 6-24 months determined that 89% of children seroconverted to all three vaccine strains during both years.[82] During year 1, among 411 children, vaccine efficacy was 66% (95% confidence interval [CI] = 34%-82%) against culture-confirmed influenza (attack rates: 5.5% and 15.9% among vaccine and placebo groups, respectively). During year 2, among 375 children, vaccine efficacy was -7% (CI = -247%-67%; attack rates: 3.6% and 3.3% among vaccine and placebo groups, respectively); the second year exhibited lower attack rates overall and was considered a mild season. In both years of this study, the vaccine strains were well- matched to the circulating influenza virus strains.

A randomized study among children aged 1-15 years also demonstrated that inactivated influenza vaccine was 77% and 91% effective against influenza respiratory illness during H3N2 and H1N1 years, respectively.[71] One study documented a vaccine efficacy of 56% against influenza illness among healthy children aged 3-9 years,[83] and another study determined vaccine efficacy against influenza type B infection and influenza type A infection of 22%-54% and 60%-78% among children with asthma aged 2-6 years and 7-14 years, respectively.[84] Two studies have documented that TIV vaccine decreases the incidence of influenza-associated otitis media among young children by approximately 30%,[16,17] whereas a third study determined that vaccination did not reduce the burden of acute otitis media.[82]

Effectiveness of One Dose versus Two Doses of Influenza Vaccine Among Previously Unvaccinated Children Aged <9 Years. Vaccine effectiveness is lower among previously unvaccinated children aged <9 years if they have only received 1 dose of influenza vaccine, compared with children who have received 2 doses. A retrospective study among approximately 5,000 children aged 6-23 months conducted during a year with a suboptimal vaccine match indicated vaccine effectiveness of 49% against medically attended, clinically diagnosed pneumonia or influenza among childrenwho had received 2 doses of influenza vaccine. No effectiveness was demonstrated among children who had received only 1 dose of influenza vaccine, illustrating the importance of administering 2 doses of vaccine to previously unvaccinated children aged <9 years.[85] Similar results were observed in a case-control study of children aged 6-59 months with laboratory-confirmed influenza (86). A study assessing protective antibody responses after 1 and 2 doses of vaccine among vaccine-naive children aged 5-8 years also demonstrated the importance of compliance with the 2-dose recommendation.[87] When the vaccine antigens do not change from one season to the next, priming with a single dose of vaccine in the spring, followed by a dose in the fall might result in similar antibody responses to a 2-dose regimen in the fall.[88,89]

Adults Aged <65 Years. When the vaccine and circulating viruses are antigenically similar, influenza vaccine typically prevents influenza illness among approximately 70%-90% of healthy adults aged <65 years.[9,12,90,91] Vaccination of healthy adults also has resulted in decreased work absenteeism and decreased use of health-care resources, including use of antibiotics, when the vaccine and circulating viruses are well-matched.[9,10,11,12,91,92] In a case-control study of adults aged 50-64 years with laboratory-confirmed influenza during the 2003-04 season when the vaccine and circulating viruses were not well-matched, vaccine effectiveness was estimated to be 52% among healthy persons and 38% among those with one or more high-risk conditions.[93]

Adults Aged ≥65 Years. An important benefit of the influenza vaccine is its ability to help prevent secondary complications and reduce the risk for influenza-related hospitalization and death among adults aged ≥65 years with and without high-risk medical conditions (e.g., heart disease and diabetes).[13,14,15,18,94,95] Older persons and persons with certain chronic diseases might have lower postvaccination antibody titers than healthy young adults and can remain susceptible to influenza virus infection and influenza-related upper respiratory tract illness.[96,97,98] A randomized trial among noninstitutionalized persons aged ≥60 years reported a vaccine efficacy of 58% against influenza respiratory illness but indicated that efficacy might be lower among those aged ≥70 years.[99] However, among older persons not living in nursing homes or similar chronic-care facilities, influenza vaccine is 30%-70% effective in preventing hospitalization for pneumonia and influenza.[15,100] Among older persons who reside in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications, and deaths. In this population, the vaccine can be 50%-60% effective in preventing influenza-related hospitalization or pneumonia and 80% effective in preventing influenza-related death, although the effectiveness in preventing influenza illness often ranges from 30% to 40%.[101,102,103]

The immunogenicity of the approved LAIV has been assessed in multiple studies,[104,105,106,107,108,109,110] which included approximately 100 children aged 5-17 years and approximately 300 adults aged 18-49 years. LAIV virus strains replicate primarily in nasopharyngeal epithelial cells. The protective mechanisms induced by vaccination with LAIV are not completely understood but appear to involve both serum and nasal secretory antibodies. No single laboratory measurement closely correlates with protective immunity induced by LAIV.

Healthy Children. A randomized, double-blind, placebo-controlled trial among 1,602 healthy children initially aged 15-71 months assessed the efficacy of trivalent LAIV against culture-confirmed influenza during two seasons.[111,112] This trial included subsets of 238 healthy children (163 vaccinees and 75 placebo recipients) aged 60-71 months who received 2 doses and 74 children (54 vaccinees and 20 placebo recipients) aged 60-71 months who received a single dose during season one, and a subset of 544 children (375 vaccinees and 169 placebo recipients) aged 60-84 months during season two. Children who continued in the study remained in the same study group. In season one, when vaccine and circulating virus strains were well-matched, efficacy was 93% for participants who received 2 doses of LAIV. In season two, when the A (H3N2) component was not well-matched between vaccine and circulating virus strains, efficacy was 86% overall. The vaccine was 92% efficacious in preventing culture-confirmed influenza during the two-season study. Other results included a 27% reduction in febrile otitis media and a 28% reduction in otitis media with concomitant antibiotic use. Receipt of LAIV also resulted in 21% fewer febrile illnesses. A review of LAIV effectiveness in children aged 18 months-18 years found effectiveness against MAARI of 18% but greater estimated efficacy levels: 92% against influenza A (H1N1) and 66% against an influenza B drift variant.[113]

Healthy Adults. A randomized, double-blind, placebo-controlled trial among 4,561 healthy working adults aged 18-64 years assessed multiple endpoints, including reductions in self-reported respiratory tract illness without laboratory confirmation, absenteeism, health-care visits, and medication use during peak and total influenza outbreak periods.[114] The study was conducted during the 1997-98 influenza season, when the vaccine and circulating A (H3N2) strains were not well-matched. During peak outbreak periods, no difference in febrile illnesses between LAIV and placebo recipients was observed. However, vaccination was associated with reductions in severe febrile illnesses of 19% and febrile upper respiratory tract illnesses of 24%. Vaccination also was associated with fewer days of illness, fewer days of work lost, fewer days with health-care-provider visits, and reduced use of prescription antibiotics and over-the-counter medications. Among a subset of 3,637 healthy adults aged 18-49 years, LAIV recipients (n = 2,411) had 26% fewer febrile upper-respiratory illness episodes; 27% fewer lost work days as a result of febrile upper respiratory illness; and 18%-37% fewer days of health-care-provider visits caused by febrile illness, compared with placebo recipients (n = 1,226). Days of antibiotic use were reduced by 41%-45% in this age subset.

A randomized, double-blind, placebo-controlled challenge study among 92 healthy adults (LAIV, n = 29; placebo, n = 31; inactivated influenza vaccine, n = 32) aged 18-41 years assessed the efficacy of both LAIV and inactivated vaccine.[115] The overall efficacy of LAIV and inactivated influenza vaccine in preventing laboratory-documented influenza from all three influenza strains combined was 85% and 71%, respectively, on the basis of experimental challenge by viruses to which study participants were susceptible before vaccination. The difference in efficacy between the two vaccines was not statistically significant.


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