Use Of Live Attenuated Influenza Vaccine Research Articles

Recommendations for Prevention and Control of Influenza in Children, 2021-2022.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2021–2022 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report.1 The American Academy of Pediatrics recommends annual influenza immunization of all children without medical contraindications, starting at 6 months of age. Influenza vaccination is an important intervention to protect vulnerable populations and reduce the burden of respiratory illnesses during circulation of severe acute respiratory syndrome coronavirus 2, which is expected to continue during the 2021–2022 influenza season. Any licensed, recommended, age-appropriate vaccine available can be administered, without preference for one product or formulation over another. Antiviral treatment of influenza with any licensed, recommended, age-appropriate influenza antiviral medication is recommended for children with suspected or confirmed influenza who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza. Antiviral treatment may be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications, in whom an influenza diagnosis is confirmed or suspected, if treatment can be initiated within 48 hours of illness onset and for children whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza.Children consistently have the highest attack rates of influenza in the community during seasonal influenza epidemics. Children play a pivotal role in the transmission of influenza virus infection to household and other close contacts and can experience substantial morbidity, including severe or fatal complications from influenza infection.2 Children younger than 5 years, especially those younger than 2 years, and children with certain underlying medical conditions are at increased risk of hospitalization and complications attributable to influenza (Table 1).2 School-aged children bear a large influenza disease burden and are more likely to seek influenza-related medical care compared with healthy adults.2,3 Reducing influenza virus transmission among children decreases the burden of childhood influenza and transmission of influenza virus to household contacts and community members of all ages.2,3 Influenza vaccination is particularly important during the severe acute respiratory syndrome coronavirus 2 pandemic to reduce the burden of respiratory illnesses and hospitalizations and preserve the capacity of the health care infrastructure. The American Academy of Pediatrics (AAP) recommends routine influenza vaccination and antiviral agents for the prevention and treatment of influenza in children, respectively. This policy statement summarizes updates and recommendations for the 2021–2022 influenza season. An accompanying technical report provides further detail regarding recent influenza seasons, influenza vaccine effectiveness (VE), detailed updates of inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs), influenza vaccination coverage, vaccine implementation, and timing of vaccination and duration of protection.1Children and adolescents with certain underlying medical conditions have a high risk of complications from influenza (Table 1). Although universal influenza vaccination is recommended for everyone starting at 6 months of age, emphasis should be placed in ensuring that high-risk and vulnerable children and their household contacts and caregivers receive annual influenza vaccine.The seasonal influenza vaccines licensed for children and adults for the 2021–2022 season are shown in Table 2. More than one product may be appropriate for a given patient, and vaccination should not be delayed to obtain a specific product.All 2021–2022 seasonal influenza vaccines will be quadrivalent and contain the same influenza strains as recommended by the World Health Organization and the US Food and Drug Administration Vaccines and Related Biological Products Advisory Committee for the Northern Hemisphere.4,5 Both influenza A(H1N1) and A(H3N2) components are different in this season’s vaccine. The B components are unchanged. The influenza A strains may be different for egg-based versus cell- or recombinant-based vaccines on the basis of their optimal characteristics for each platform, but all are matched to the strains expected to circulate in the 2021–2022 season.The contraindications and precautions for the use of IIV and LAIV are described in Table 3, and further details are provided in the technical report.1 Anaphylactic and severe allergic reactions to any influenza vaccine are contraindications to vaccination. The AAP recommends that children who have had an allergic reaction after a previous dose of any influenza vaccine should be evaluated by an allergist to determine if future receipt of the vaccine is appropriate.Antivirals available for the treatment and prophylaxis of influenza in children are described in Table 4.Antiviral chemoprophylaxis is recommended after known or suspected influenza exposure in the following situations: Jennifer M. Frantz, MPH

The effect of live attenuated influenza vaccine on pneumococcal colonisation densities among children aged 24–59 months in The Gambia: a phase 4, open label, randomised, controlled trial

SummaryBackgroundInfluenza and other respiratory viruses promote Streptococcus pneumoniae proliferation in the upper respiratory tract. We sought to investigate for what we believe is the first time, the effect of intranasal live attenuated influenza vaccine (LAIV) on nasopharyngeal S pneumoniae density in a low-income to middle-income country population with high pneumococcal carriage rates.MethodsIn an open-label, randomised, controlled trial in The Gambia, 330 healthy children aged 24–59 months were randomly assigned 2:1 to receive one trivalent LAIV dose at enrolment (day 0, intervention) or at the end of active follow-up (day 21, control). The investigator team were initially masked to block size and randomisation sequence to avoid allocation bias. Group allocation was later revealed to the investigator team. The primary outcome was PCR-quantified day 7 and 21 pneumococcal density. Asymptomatic respiratory viral infection at baseline and LAIV strain shedding were included as covariates in generalised mixed-effects models, to assess the effect of LAIV and other variables on pneumococcal densities. The study is registered at ClinicalTrials.gov, NCT02972957, and is closed to recruitment.FindingsBetween Feb 8 and April 12, 2017, and Jan 15 and March 28, 2018, of 343 children assessed for eligibility, 213 in the intervention group and 108 in the control group completed the study and were included in the final analysis. Although no significant differences were seen in pneumococcal carriage or density at each timepoint when comparing groups, changes from baseline were observed in the LAIV group. The baseline S pneumoniae carriage prevalence was high in both LAIV and control groups (75%) and increased by day 21 in the LAIV group (85%, p=0·0037), but not in the control group (79%, p=0·44). An increase in pneumococcal density from day 0 amounts was seen in the LAIV group at day 7 (+0·207 log10 copies per μL, SE 0·105, p=0·050) and day 21 (+0·280 log10 copies per μL, SE 0·105, p=0·0082), but not in the control group. Older age was associated with lower pneumococcal density (−0·015 log10 copies per μL, SE 0·005, p=0·0030), with the presence of asymptomatic respiratory viruses at baseline (+0·259 log10 copies per μL, SE 0·097, p=0·017), and greater LAIV shedding at day 7 (+0·380 log10 copies per μL, SE 0·167, p=0·024) associated with higher pneumococcal density. A significant increase in rhinorrhoea was reported in the LAIV group compared with the control group children during the first 7 days of the study (103 [48%] of 213, compared with 25 [23%] of 108, p<0·0001), and between day 7 and 21 (108 [51%] of 213, compared with 28 [26%] of 108, p<0·0001).InterpretationLAIV was associated with a modest increase in nasopharyngeal pneumococcal carriage and density in the 21 days following vaccination, with the increase in density lower in magnitude than previously described in the UK. This increase was accelerated when LAIV was administered in the presence of pre-existing asymptomatic respiratory viruses, suggesting that nasopharyngeal S pneumoniae proliferation is driven by cumulative mixed-viral co-infections. The effect of LAIV on pneumococcal density is probably similar to other respiratory viral infections in children. Our findings provide reassurance for the use of LAIV to expand influenza vaccine programmes in low-income to middle-income country populations with high pneumococcal carriage.FundingWellcome Trust.

Detrimental impact of allergic airway disease on live attenuated influenza vaccine.

Historically, live attenuated, as opposed to inactivated, vaccines have been highly successful against many infectious diseases (see Ref. 1). However, curiously, seasonal live attenuated influenza vaccines (LAIV) or “Flumist” have not demonstrated superior efficacy when compared to inactivated influenza vaccines (IIV), especially in the past several influenza seasons.2, 3 This is in striking contrast to animal models in which Flumist consistently exhibits a clear advantage over IIV in inducing not only robust humoral immunity but also cytotoxic T cell immunity,4-7 which is believed to be important in cross-protection against mismatched influenza viruses.8-11 The reason for this discrepancy between human and animal data is not fully understood, but host factors have been suggested to contribute to highly variable LAIV efficacy.12 Given that chronic conditions, such as asthma, are highly prevalent among adults, that is, 1 in 13 (7.7%) adults in the United States according to centers for disease control and prevention (CDC),13 we propose that they can negatively impact vaccine efficacy. To test our hypothesis, we utilized mouse models of allergic airway disease (AAD) to assess LAIV efficacy in asthmatic mice (Figure 1A). LAIV-elicited systemic IgG responses were significantly diminished in AAD mice (Figure 1B,C). Antibody class switching is a complex process that involves a number of different stimuli.14 In particular, cytokines are known stimuli that direct antibody isotype switching. For example, the type 1 cytokine IFN-γ drives class switching to IgG2a and the type 2 cytokine IL-4 promotes switching to IgG1.15 Since mouse models of asthma are known to trigger type 2-biased immune responses,16, 17 it is plausible that the type 2 cytokine environment in AAD mice is suppressing type 1 immunity-based LAIV. Indeed, analysis of IgG subclasses shows that type 1 immunity-associated IgG2a was downregulated in AAD mice following intranasal (i.n.) LAIV vaccination (Figure 1B,C). Consistent with the systemic antibody profile, mucosal IgG and IgG2a antibodies were also suppressed in AAD mice (Figure 1D). In addition, mucosal IgA titer was reduced in mice with AAD (Figure 1D). We next investigated the protective efficacy of LAIV in AAD vs non-AAD mice. While LAIV-immunized AAD mice were protected against homologous challenge (data not shown), the cross-protective efficacy against heterologous infection was severely compromised (Figure 1E). This observation is consistent with our previous report that live influenza virus infection establishes inferior mucosal antibody immunity in AAD mice.18 Taken together, our results show that AAD is a host-associated factor that can negatively impact LAIV efficacy. Our finding may help explain why LAIV efficacy is highly variable in humans. The implication of our finding is that vaccine research should consider the impact of host factors such as chronic diseases for evaluation of experimental vaccines because the magnitude of interference may differ depending on the vaccine type. It is important to note that LAIV is not recommended for individuals with asthma due to increased incidence of wheezing post LAIV administration.19, 20 Further, people with severe asthma are often excluded from clinical trials that evaluate LAIV efficacy. Therefore, the use of LAIV among asthmatics has been relatively limited and whether asthma exacerbation has a negative effect on the efficacy of LAIV in humans remains unknown. In addition to asthma, other conditions that induce lung inflammation may also impact the efficacy of LAIV, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.21, 22 SARS-CoV-2 is particularly concerning given the high prevalence of asymptomatic infections, and therefore vaccine recipients may unknowingly receive LAIV vaccination while infected with SARS-CoV-2. Further research efforts are clearly warranted to elucidate the precise mechanism by which allergic lung inflammation interferes with the B cell immunogenicity of LAIV. Knowing the detrimental immune pathway that exists in AAD mice may help design a better vaccination approach to circumvent the negative interference imposed by host factors. Yoichi Furuya is supported by R56 AI146434 and American Heart Association Scientist Development Grant. Yoichi Furuya and Sreeja Roy are supported through The American Association of Immunologists Careers in Immunology Fellowship Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no competing interests. Conceptualization: Yoichi Furuya, Sreeja Roy Data Curation: Yoichi Furuya, Clare M. Williams Formal Analysis: Yoichi Furuya Funding Acquisition: Yoichi Furuya Writing—Original Draft Preparation: Yoichi Furuya, Sreeja Roy, Clare M. Williams Writing—Review & Editing: Yoichi Furuya, Sreeja Roy, Clare M. Williams Yoichi Furuya had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. The data that support the findings of the study are available from the corresponding author upon request.

Immune Responses Elicited by Live Attenuated Influenza Vaccines as Correlates of Universal Protection against Influenza Viruses.

Influenza virus infection remains a major public health challenge, causing significant morbidity and mortality by annual epidemics and intermittent pandemics. Although current seasonal influenza vaccines provide efficient protection, antigenic changes of the viruses often significantly compromise the protection efficacy of vaccines, rendering most populations vulnerable to the viral infection. Considerable efforts have been made to develop a universal influenza vaccine (UIV) able to confer long-lasting and broad protection. Recent studies have characterized multiple immune correlates required for providing broad protection against influenza viruses, including neutralizing antibodies, non-neutralizing antibodies, antibody effector functions, T cell responses, and mucosal immunity. To induce broadly protective immune responses by vaccination, various strategies using live attenuated influenza vaccines (LAIVs) and novel vaccine platforms are under investigation. Despite superior cross-protection ability, very little attention has been paid to LAIVs for the development of UIV. This review focuses on immune responses induced by LAIVs, with special emphasis placed on the breadth and the potency of individual immune correlates. The promising prospect of LAIVs to serve as an attractive and reliable vaccine platforms for a UIV is also discussed. Several important issues that should be addressed with respect to the use of LAIVs as UIV are also reviewed.

Use of High-Dose Influenza and Live Attenuated Influenza Vaccines by US Primary Care Physicians

Several different types of influenza vaccine are licensed for use in adults in the USA including high-dose inactivated influenza vaccine (HD-IIV) and live attenuated influenza vaccine (LAIV). HD-IIV is licensed for use in adults ≥ 65years, and recommendations for use of LAIV have changed several times in recent years. We sought to examine family physicians' (FPs) and general internal medicine physicians' (GIMs) perceptions, knowledge, and practices for use of HD-IIV and LAIV during the 2016-2017 and 2018-2019 influenza seasons. E-mail and mail surveys conducted February-March 2017, January-February 2019. Nationally representative samples of FPs and GIMs. Surveys assessed HD-IIV practices (2017), knowledge and perceptions (2019), and LAIV knowledge and practices (2017, 2019). Response rates were 67% (620/930) in 2017 and 69% (642/926) in 2019. Many physicians believed HD-IIV is more effective than standard dose IIV in patients ≥ 65years (76%) and reported their patients ≥ 65years believe they need HD-IIV (67%). Most respondents incorrectly thought ACIP preferentially recommends HD-IIV for adults ≥ 65years (88%); 65% "almost always/always" recommended HD-IIV for adults ≥ 65years. Some physicians incorrectly thought ACIP preferentially recommends HD-IIV for adults < 65years with cardiopulmonary disease (38%) or immunosuppression (48%); some respondents recommended HD-IIV for these groups (25% and 28% respectively). In 2017, 88% of respondents knew that ACIP recommended against using LAIV during the 2016-2017 influenza season, and 4% recommended LAIV to patients. In 2019, 63% knew that ACIP recommended that LAIV could be used during the 2018-2019 influenza season, and 8% recommended LAIV. Many physicians incorrectly thought ACIP had preferential recommendations for HD-IIV. Physicians should be encouraged to use any available age-appropriate influenza vaccine to optimize influenza vaccination particularly among older adults and patients with chronic conditions who are more vulnerable to severe influenza disease.

Summary of the NACI systematic review and recommendation on the use of live attenuated influenza vaccine (LAIV) in HIV-infected individuals

Annual influenza vaccination is recommended for all individuals six months of age and older, including those with HIV infection. Prior to this statement, the National Advisory Committee on Immunization (NACI) stated that live attenuated influenza vaccine (LAIV) was contraindicated for all individuals with HIV infection. The objective of this article is to update NACI's guidance on the use of LAIV for HIV-infected individuals. A systematic literature review of the use of LAIV in individuals with HIV was undertaken. The Canadian Adverse Events Following Immunization Surveillance System was searched for reports of adverse events following vaccination with LAIV in HIV-infected individuals. NACI approved the revised recommendations. NACI concluded that LAIV is immunogenic in children with HIV, and available data suggest that it is safe, although data were insufficient to detect possible uncommon adverse effects. LAIV may be considered as an option for vaccination of children 2-17 years old who meet the following criteria: 1) receiving highly active antiretroviral therapy for at least four months; 2) CD4 count of 500/µL or greater if age 2-5 years, or of 200/µL or greater if age 6-17 years; and 3) HIV plasma RNA less than 10,000 copies/mL. LAIV remains contraindicated for adults with HIV because of insufficient data. Intramuscular influenza vaccination is considered the standard for children living with HIV by NACI and the Canadian Paediatric & Perinatal HIV/AIDS Research Group, particularly for those without HIV viral load suppression (i.e. plasma HIV RNA is 40 copies/mL or greater). However, if intramuscular (IM) vaccination is not accepted by the patient or substitute decision-maker, LAIV would be reasonable for children meeting the criteria listed above. LAIV may be considered as an option for annual vaccination of selected children with HIV.

Live Attenuated Influenza Vaccine: Is Past Performance a Guarantee of Future Results?

Live attenuated influenza vaccine (LAIV) has had a tumultuous recent history that can be difficult for many to follow and understand. Prior to 2013, LAIV had a record of accomplishment of providing equal or superior protection against influenza in children. Since 2013, concerns about the lack of protection with LAIV against pandemic H1N1 strains led to the withdrawal of any recommendation for use in the US by the Advisory Committee on Immunization Practices (ACIP). After some significant changes to the content, evaluation and production of LAIV, it has been be recommended again for use in the US in 2018-19. This commentary reviews the origin of LAIV, the events and circumstances that led to the withdrawal of any recommendation for LAIV use by the ACIP, the merits, shortcomings and repercussions of that decision and finally offers some thoughts about the future of LAIV.

Vaccine recommendations for children and youth for the 2017/2018 influenza season.

The Canadian Paediatric Society continues to encourage annual influenza vaccination for ALL children and youth ≥6 months of age. Recommendations from the National Advisory Committee on Immunization (NACI) for the 2017/2018 influenza season are not substantially changed from those of last season. NACI has conducted a review of all available vaccine effectiveness data concerning live attenuated influenza vaccine (LAIV) and concludes that current evidence supports the continued use of LAIV in Canada, although use is not currently recommended in the USA because of concern about efficacy.

Intranasal influenza vaccine: Why does Canada have different recommendations from the USA on its use?

Canada and the USA differ in their recommendations for the use of live attenuated influenza vaccine (LAIV). The Canadian National Advisory Committee on Immunization (NACI) continues to recommend LAIV as one of the influenza vaccines available for use in children 2 to 17 years of age. The US Advisory Committee on Immunization Practices (ACIP) made an interim recommendation against the use of LAIV for the 2016 to 2017 influenza season in response to low LAIV effectiveness observed in the USA during the 2013 to 2014 to 2015 to 2016 seasons. The recommendation has been continued for the 2017 to 2018 season. In response, NACI undertook a review of available LAIV effectiveness data in children and adolescents from Canada, the USA and a number of European countries. This commentary by Canada's Chief Public Health Officer summarizes the findings of that review and provides the rationale for Canada's current continued recommendation for LAIV use.

The safety of live attenuated influenza vaccine in children and adolescents 2 through 17years of age: A Vaccine Safety Datalink study.

To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17years of age. The study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR>2.0 regardless of statistical significance, manual medical record review was performed to confirm case status. During the study period, 396173 children received 590018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses. In a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.

Summary of the NACI Statement on Seasonal Influenza Vaccine for 2017-2018.

Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC). To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2017-2018 influenza season. Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations. The recommendations include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). The annual statement has been updated for the 2017-2018 influenza season to incorporate recommendations for the use of live attenuated influenza vaccine (LAIV) that were contained in two addenda published after the 2016-2017 statement. These recommendations were 1) that egg-allergic individuals may be vaccinated against influenza using the low ovalbumin-containing LAIV licensed for use in Canada and 2) to continue to recommend the use of LAIV in children and adolescents 2-17 years of age, but to remove the preferential recommendation for its use. NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, and others as indicated.

Live attenuated influenza vaccine use and safety in children and adults with asthma

BackgroundLive attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing. ObjectiveTo describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population. MethodsWe identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008–2009 through 2010–2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old. ResultsIn our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63–1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48–1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV. ConclusionLAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events.

2014-2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type.

Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory Committee on Immunization Practices recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years. Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval [CI], 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, -16% to 38%) for IIV and -3% (CI, -50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV. The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.

Effectiveness of the live attenuated and the inactivated influenza vaccine in two-year-olds - a nationwide cohort study Finland, influenza season 2015/16.

Although widely recommended, influenza vaccination of children is part of the national vaccination programme only in few countries. In addition to Canada and the United States (US), in Europe Finland and the United Kingdom have introduced live attenuated influenza vaccine (LAIV) for healthy children in their programmes. On 22 June 2016, the US Advisory Committee on Immunizations Practices, voted against further use of LAIV due to no observed vaccine effectiveness (VE) over three consecutive influenza seasons (2013/14 to 2015/16). We summarise the results of a nationwide, register-based cohort study (N=55,258 of whom 8,086 received LAIV and 4,297 TIV); all outcome (laboratory-confirmed influenza), exposure (vaccination) and confounding variable data were retrieved from four computerised national health registers, which were linked via a unique personal identity code assigned to all permanent Finnish residents regardless of nationality. Our study provides evidence of moderate effectiveness against any laboratory-confirmed influenza of the quadrivalent LAIV vaccine (VE: 51%; 95% confidence interval (CI): 28–66%) as well as the inactivated trivalent vaccine (VE: 61%; 95% CI: 31–78%) among two-year-olds during the influenza season 2015/16 in Finland. Based on these data, Finland will continue using LAIV for young children in its National Immunisation Programme this coming influenza season.

Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2016-2017.

Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (the Agency). To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2016-2017 influenza season. Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI, based on NACI's evidence-based process for developing recommendations, and include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency's website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). The annual NACI seasonal influenza vaccine recommendations have been updated for the 2016-2017 influenza season to include adults with neurologic or neurodevelopment conditions among the groups for whom influenza vaccination is particularly recommended; to include the new high-dose, trivalent inactivated influenza vaccine for use in adults 65 years of age and over; to recommend that egg-allergic individuals may also be vaccinated against influenza using the low ovalbumin-containing live attenuated influenza vaccine (LAIV) licensed for use in Canada (NACI has previously recommended that egg-allergic individuals may be vaccinated using inactivated influenza vaccines); and to remove the preferential recommendation for the use of LAIV in children 2-17 years of age. Two addenda to the 2016-2017 Statement address these new LAIV recommendations. NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk and others as indicated.

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.

Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV.

Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2015-2016.

The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to immunization. To summarize the update of the 2015-2016 recommendations by NACI regarding the use of seasonal influenza vaccines. Annual influenza vaccine recommendations are developed by the Influenza Working Group for consideration by NACI, based on NACI's evidence-based process for developing recommendations, and includes: a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity, and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. NACI continues to recommend influenza vaccination for all individuals aged 6 months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, and others as indicated. For the 2015-2016 influenza season, the Statement has been updated to identify children and adolescents with neurologic or neurodevelopment conditions as a group at high risk for influenza-related complications or hospitalization. Several changes to product availability in Canada have also been noted. A new adjuvanted, trivalent influenza vaccine (Fluad Pediatric™ [Novartis]) will be available for use in children aged 6 to <24 months. The recommended choice of product for this age group, however, is quadrivalent inactivated influenza vaccine (QIV), because children are more likely to be affected by influenza B, and the QIV provides broader protection against both lineages of influenza B. If QIV is not available, either unadjuvanted or adjuvanted trivalent inactivated influenza vaccine (TIV) should be used. Only the quadrivalent formulation of the live attenuated influenza vaccine (LAIV) (FluMist® Quadrivalent [AstraZeneca]) will be available, and the recommendation for preferential use of LAIV in children 2 to 17 years of age who do not have contraindications to this vaccine remains unchanged following a review of information pertaining to reports of decreased effectiveness of LAIV in the United States during the 2013-2014 season. Finally, the intradermal trivalent influenza vaccine (Intanza® [Sanofi Pasteur]) will no longer be available for use in Canada. Other updates to the Statement include additional information reaffirming the safety of LAIV use in children with cystic fibrosis who are not considered immunosuppressed or receiving immunosuppressive treatment, as well as a revised definition for oculo-respiratory syndrome which, when it occurs, should be reported as an adverse event following immunization (AEFI) to local public health officials. Vaccination is the safest, longest lasting and most effective way to prevent influenza.

Acceptability of live attenuated influenza vaccine by vaccine providers in Quebec, Canada

A live attenuated influenza vaccine (LAIV) was offered during the 2012-13 influenza season in Quebec, Canada, to children aged between 2 and 17 years with chronic medical conditions. Despite the offer, uptake of the vaccine was low. We assessed the perceptions and opinions about seasonal influenza vaccination and LAIV use among vaccine providers who participated in the 2012-13 campaign. More than 70% of them thought that LAIV was safe and effective and more than 90% considered that the vaccine was well-received by parents and healthcare professionals. According to respondents, the most frequent concerns of parents about LAIV were linked to vaccine efficacy. LAIV is well-accepted by vaccine providers involved in influenza vaccination clinics, but more information about the vaccine and the recommendations for its use are needed to increase vaccine uptake.

Erratum to: Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2–6 years in Germany

Erratum to: Background paper to the recommendation for the preferential use of live-attenuated influenza vaccine in children aged 2–6 years in Germany