Doses Of Inactivated Influenza Vaccine Research Articles

Protective and vaccine dose-sparing efficacy of Poly I:C-functionalized calcium phosphate nanoparticle adjuvants in inactivated influenza vaccination

Adjuvants are required to increase the immunogenicity and efficacy of vaccination and enable vaccine dose sparing. Polyinosinic-polycytidylic acid (Poly I:C), a toll-like receptor 3 agonist, is a promising adjuvant candidate that can induce cell-mediated immune responses; however, it remains unlicensed owing to its low stability and toxicity. Calcium phosphate (CaP), a biocompatible and biodegradable nanoparticle, is widely used in biomedicine for stable and targeted drug delivery. In this study, we developed Poly I:C-functionalized CaP (Poly-CaP) and evaluated its vaccine adjuvant efficacy in vitro and in vivo. A half dose of Poly-CaP nanoparticles showed similar efficacy to a full dose of soluble Poly I:C in stimulating bone marrow-derived dendritic cells and macrophages to secrete proinflammatory cytokines and express their activation markers. Immunization with a half dose of inactivated influenza vaccine in the presence of Poly I:C or Poly-CaP adjuvants induced sufficient antigen-specific humoral responses after boost immunization. Immunization with Poly I:C, CaP, or Poly-CaP-adjuvanted with a half dose of influenza vaccine showed comparable protective efficacy against lethal virus infection, with lower weight loss and virus titer than a full dose of influenza vaccine. The Poly-CaP adjuvant was effective in stimulating antigen-specific CD4+ T cell proliferation in the lungs. Collectively, our results showed that the Poly-CaP adjuvant enhanced antigen-specific cell-mediated immunity and humoral immune responses with vaccine dose-sparing effects, suggesting its potential as a novel vaccine adjuvant candidate.

Antibody Response and Protection After Receipt of Inactivated Influenza Vaccine: A Systematic Review.

Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of age receiving the vaccine for the first time. To systematically review studies comparing vaccine effectiveness (VE) and immunogenicity after 1 or 2 doses of inactivated influenza vaccine (IIV) in children. Data sources included Medline, Embase, and Cochrane Library databases. We included studies published in a peer reviewed journal up to April 2, 2019, with available abstracts, written in English, and with children aged 6 months through 8 years. VE among fully and partially vaccinated children was compared with that of unvaccinated children. We extracted geometric mean titers of serum hemagglutination inhibition (HAI) antibodies against influenza A(H1N1), A(H3N2), and B-lineage vaccine antigens after 1 and 2 IIV doses. Outcomes were evaluated by age, timing of doses, vaccine composition, and prevaccination titers. A total of 10 VE and 16 immunogenicity studies were included. VE was higher for fully vaccinated groups than partially vaccinated groups, especially for children aged 6-23 months. Our findings show increased HAI titers after 2 doses, compared with 1. Older children and groups with prevaccination antibodies have robust HAI titers after 1 dose. Similar vaccine strains across doses, not the timing of doses, positively affects immune response. Few studies focused on older children. Researchers typically administered one-half the standard dose of IIV. HAI antibodies are an imperfect correlate of protection. Findings support policies recommending 2 IIV doses in children to provide optimal protection against influenza.

Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: A 2-year, randomized, triple-blind, placebo-controlled trial.

BackgroundInfluenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.Methods and findingsIn June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years.Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year.In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.ConclusionsIn this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.Trial registrationClinical Trials Registry of India CTRI/2015/06/005902.

Patterns of Influenza Vaccination and Vaccine Effectiveness Among Young US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness

The burden of influenza among young children is high, and influenza vaccination is the primary strategy to prevent the virus and its complications. Less is known about differences in clinical protection following 1 vs 2 doses of initial influenza vaccination. To describe patterns of influenza vaccination among young children who receive outpatient care for acute respiratory tract illness in the US and compare vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza by number of influenza vaccine doses received. This test-negative case-control study was conducted in outpatient clinics, including emergency departments, at 5 sites of the US Influenza Vaccine Effectiveness Network during the 2014-2015 through 2017-2018 influenza seasons. The present study was performed from November 5, 2014, to April 12, 2018, during periods of local influenza circulation. Children aged 6 months to 8 years with an acute respiratory tract illness with cough who presented for outpatient care within 7 days of illness onset were included. All children were tested using real-time, reverse-transcriptase polymerase chain reaction for influenza for research purposes. Vaccination in the enrollment season with either 1 or 2 doses of inactivated influenza vaccine as documented from electronic medical records, including state immunization information systems. Medically attended acute respiratory tract infection with real-time, reverse-transcriptase polymerase chain reaction testing for influenza. Of 7533 children, 3480 children (46%) were girls, 4687 children (62%) were non-Hispanic white, and 4871 children (65%) were younger than 5 years. A total of 3912 children (52%) were unvaccinated in the enrollment season, 2924 children (39%) were fully vaccinated, and 697 children (9%) were partially vaccinated. Adjusted VE against any influenza was 51% (95% CI, 44%-57%) among fully vaccinated children and 41% (95% CI, 25%-54%) among partially vaccinated children. Among 1519 vaccine-naive children aged 6 months to 2 years, the VE of 2 doses in the enrollment season was 53% (95% CI, 28%-70%), and the VE of 1 dose was 23% (95% CI, -11% to 47%); those who received 2 doses were less likely to test positive for influenza compared with children who received only 1 dose (adjusted odds ratio, 0.57; 95% CI, 0.35-0.93). Consistent with US influenza vaccine policy, receipt of the recommended number of doses resulted in higher VE than partial vaccination in 4 influenza seasons. Efforts to improve 2-dose coverage for previously unvaccinated children may reduce the burden of influenza in this population.

Conventional influenza vaccines influence the performance of a universal influenza vaccine in mice

Universal influenza vaccines are designed to protect against diverse strains of influenza virus. Preclinical testing of new vaccine candidates is usually done in naïve animals, despite intended use in the human population with its varied immune history including responses to previous vaccinations. As an approach more relevant to human use, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group was given two intranasal doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal influenza vaccine: recombinant adenoviruses expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) (A/NP + M2-rAd). Immune responses to universal vaccine antigens A/NP and M2 were assessed by ELISA and interferon-γ ELISPOT. Protection was tested by challenge with mouse-adapted A/FM/1/47 (H1N1) and monitoring for weight loss and survival. Universal vaccine performance was enhanced, inhibited or unaffected by particular prior vaccinations. Mice given Afluria IIV and LAIV had greater antibody and T-cell response to A/NP than mice without prior vaccination, providing examples of enhanced A/NP + M2-rAd performance. Though Fluvirin IIV partially inhibited, the universal vaccine still provided considerable protection unlike conventional vaccination. Fluzone IIV and DT had no effect on A/NP + M2-rAd performance. Thus our results demonstrate that universal vaccine candidate A/NP + M2-rAd was at least partially effective in mice with diverse prior histories. However, the degree of protection and nature of the immune responses may be affected by a history of conventional vaccination and suggests that performance in humans would be influenced by immune history.

The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children.

Antipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months. Over the course of three seasons, one hundred forty-two children, receiving either a single or the first of 2 recommended doses of IIV, were randomized to receive either oral acetaminophen suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24) (open-label) immediately following IIV and every 4-8 h thereafter for 24 h. Blood samples were obtained at enrollment and 4 weeks following the last recommended IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay (HAI). Seroprotection was defined as an HAI titer ≥1:40 and seroconversion as a titer ≥1:40 if baseline titer <1:10 or four-fold rise if baseline titer ≥1:10. Participants were monitored for fever and other solicited symptoms on the day of and day following IIV. Significant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group. Significant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity.

The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial

Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat. Secondary immunogenicity outcomes are antibody titres at day 28 and percentages of seroconversion and seroprotection, all determined by haemagglutination inhibition antibody assay. The trial is completed and registered with ClinicalTrials.gov, number NCT02438423. Between June 23, 2015, and Sept 25, 2015, 100 participants were enrolled and randomly assigned to a group. There were no treatment-related serious adverse events, no treatment-related unsolicited grade 3 or higher adverse events, and no new-onset chronic illnesses. Among vaccinated groups (vaccine via health-care worker administered microneedle patch or intramuscular injection, or self-administered microneedle patch), overall incidence of solicited adverse events (n=89 vs n=73 vs n=73) and unsolicited adverse events (n=18 vs n=12 vs n=14) were similar. Reactogenicity was mild, transient, and most commonly reported as tenderness (15 [60%] of 25 participants [95% CI 39-79]) and pain (11 [44%] of 25 [24-65]) after intramuscular injection; and as tenderness (33 [66%] of 50 [51-79]), erythema (20 [40%] of 50 [26-55]), and pruritus (41 [82%] of 50 [69-91]) after vaccination by microneedle patch application. The geometric mean titres were similar at day 28 between the microneedle patch administered by a health-care worker versus the intramuscular route for the H1N1 strain (1197 [95% CI 855-1675] vs 997 [703-1415]; p=0·5), the H3N2 strain (287 [192-430] vs 223 [160-312]; p=0·4), and the B strain (126 [86-184] vs 94 [73-122]; p=0·06). Similar geometric mean titres were reported in participants who self-administered the microneedle patch (all p>0·05). The seroconversion percentages were significantly higher at day 28 after microneedle patch vaccination compared with placebo (all p<0·0001) and were similar to intramuscular injection (all p>0·01). Use of dissolvable microneedle patches for influenza vaccination was well tolerated and generated robust antibody responses. National Institutes of Health.

Conventional influenza vaccines influence the efficacy of a candidate universal influenza vaccine in mice

Abstract Universal influenza vaccines are designed to protect against diverse strains of influenza virus. In a pandemic, universal vaccines could be life-saving. Candidate vaccines are usually tested in naïve animals, despite intended use in the human population that has a varied immune history, including responses to vaccination. To be more relevant to humans, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group had two intranasal (i.n.) doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal vaccine, recombinant adenoviruses expressing influenza A NP and M2 (rAd-NP+M2, i.n.). Antibody responses to universal vaccine antigens NP and M2 were assessed by ELISA. T-cell responses to antigens were determined by IFN-γ ELISPOT. Mice were challenged with mouse-adapted A/FM/1/47 (H1N1) and subsequent weight loss determined rAd-NP+M2 efficacy. Efficacy was enhanced, inhibited or unaffected by prior history. Mice given Afluria IIV and LAIV lost less weight and had a greater antibody and T-cell response to NP than mice without prior vaccination, which are examples of enhanced rAd-NP+M2 efficacy. Inhibited vaccine efficacy was observed in mice that received Fluvirin IIV and mice had low IgG2a antibodies to NP and M2. Fluzone IIV and DT had no effect on rAd-NP+M2 efficacy. This study demonstrates that the protection by the universal influenza vaccine may be affected by a history of conventional vaccination, and suggests that performance in humans would be influenced by immune history.

The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial.

Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004–0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated.

Assessment of immune responses to H5N1 inactivated influenza vaccine among individuals previously primed with H5N2 live attenuated influenza vaccine

During the past decade, a number of H5 subtype influenza vaccines have been developed and tested in clinical trials, but most of them induced poor serum antibody responses prompting the evaluation of novel vaccination approaches. One of the most promising ones is a “prime-boost” strategy, which could result in the induction of prompt and robust immune responses to a booster influenza vaccine following priming with homologous or heterologous vaccine strains. In our study we evaluated immunogenicity of an adjuvanted A(H5N1) inactivated influenza vaccine (IIV) in healthy adult subjects who received A(H5N2) live attenuated influenza vaccine (LAIV) 1.5 years earlier and compared this with a group of naïve subjects. We found that priming with A(H5N2) LAIV induced a long-lasting B-cell immunological memory against influenza A(H5N1) virus, which was brought on by more prompt and vigorous antibody production to a single dose of A(H5N1) IIV in the primed group, compared to the naïve controls. Thus, by day 28 after the first booster dose, the hemagglutination inhibition and neutralizing (MN) antibody titer rises were 17.2 and 30.8 in the primed group, compared to 2.3 and 8.0 in the control group, respectively. The majority (79%) of the primed individuals achieved seroprotective MN antibody titers at 7 days after the first dose of the IIV. All LAIV-primed volunteers had MN titers ≥1:40 by Day 28 after one dose of IIV, whereas only 58% subjects from the naïve control group developed similar immune responses at this time point. The second A(H5N1) IIV dose did not increase the immune response in the LAIV-primed group, whereas 2 doses of IIV were required for naïve volunteers to develop significant immune responses. These findings were of special significance since Russian-based LAIV technology has been licensed to WHO, through whom the vaccine has been provided to vaccine manufacturers in India, China and Thailand — countries particularly vulnerable to a pandemic influenza. The results of our study will be useful to inform the development of vaccination strategies in these countries in the event of a pandemic

Effects of inactivated influenza vaccine on respiratory illnesses and asthma-related events in children with mild persistent asthma in Asia.

Acute asthmatic exacerbation and readmission may be associated with severe influenza infection and asthmatic children are a priority group for influenza vaccination. To date, our study is the first to evaluate the outcome of the influenza vaccine in asthmatic Asian children. To analyze the outcomes of inactivated influenza vaccine in children with mild persistent asthma A cross sectional non-randomized study was performed on 93 mild persistent asthmatic children who attended the Pediatric Allergy clinic between June 2012 in Chiang Rai Hospital and August 2013. Forty eight patients were immunized with 2 doses of inactivated influenza vaccine at one month interval. Respiratory illnesses and asthma-related events were compared between the immunized and the un-immunized groups. The two study groups had similar demographic and clinical characteristic except with regards to eczema, including asthma controllers and skin prick testing results. One year after the vaccine was administered, the immunized group had significantly reduced acute respiratory tract illnesses, asthma exacerbations, ER visits, bronchodilator usage and systemic steroid administrations. Hospitalizations (p < 0.001) and their duration (p < 0.034) were also reduced in the immunized group. Immunization of inactivated influenza vaccine in children with mild persistent asthma decreased respiratory illnesses and asthma-related events.

Immunogenicity and safety of a trivalent inactivated 2010–2011 influenza vaccine in Taiwan infants aged 6–12 months

This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6–12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6–12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6–12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6–12 months.

Absence of associations between influenza vaccines and increased risks of seizures, Guillain–Barré syndrome, encephalitis, or anaphylaxis in the 2012–2013 season

We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012-2013 influenza vaccines in the Vaccine Safety Datalink (VSD). For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6-23 months, 24-59 months, and 5-17 years) using a self-controlled risk interval design. We also monitored for Guillain-Barré syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain-Barré syndrome, encephalitis, and anaphylaxis in patients ages 2-49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site. At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012-2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012-2013 LAIV, and we thus were unable to estimate measures of relative risks. No increased risk was identified for any of the pre-specified outcomes following 2012-2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Booster and Higher Antigen Doses of Inactivated Influenza Vaccine in HIV-Infected Patients

To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.

Tiered Use of Inactivated Influenza Vaccine in the Event of a Vaccine Shortage

The United States has experienced disruptions in the manufacture or distribution of inactivated influenza vaccine during three of the last five influenza seasons. Delays in delivery of influenza vaccine or vaccine shortages remain possible, in part, because of inherent time constraints in manufacturing the vaccine, given the annual updating of influenza vaccine strains and uncertainties regarding vaccine supply (including licensure of new vaccine preparations). Although total vaccine supply for the 2005-06 influenza season is not yet known, the minimum anticipated supply is approximately 58-60 million doses of inactivated vaccine and 3 million doses of live, attenuated vaccine. This estimated supply is similar to that available during the 2004-05 season and would be adequate to satisfy historical demand for influenza vaccine among persons considered by the Advisory Committee on Immunization Practices (ACIP) to be at high risk for serious complications associated with influenza virus infection, health-care workers, and household contacts of children aged <6 months. These groups were prioritized for influenza vaccination in 2004-05. Additional doses of inactivated influenza vaccine might be available for the U.S. market in 2005-06, but this cannot yet be confirmed. Availability of additional vaccine would allow for expansion of the priority groups and, preferably, vaccination of all persons who desire it.

One for all: newer combination vaccines in practice.

As new combination vaccines are approved, practices must consider whether to switch. The decision is likely to be complex, involving everything from re-education of staff to recalculating the bottom line. At some point, however, change will be inevitable, driven principally by the need to add new vaccines to the schedule. In fall 2004, practitioners will be adding two doses of inactivated influenza vaccine to the infant schedule. More communities will be adding two doses of hepatitis A vaccine, which may become routine for all children at some point. We can hope as well for a meningococcal conjugate vaccine series, which, like Hib and PCV-7, would be administered by an infant's first birthday. In addition, there's the pentavalent bovine reassortant rotavirus vaccine (Rotateq) which, although given orally, will further crowd the schedule. The sooner we become comfortable with combination vaccines, the better.

The Influence of HIV Infection on Antibody Responses to a Two-Dose Regimen of Influenza Vaccine

We studied whether a two-dose regimen of inactivated influenza virus vaccine was more effective than a single dose in inducing protective hemagglutination-inhibition antibody responses in patients infected with human immunodeficiency virus (HIV). Participants included subjects with acquired immunodeficiency syndrome, subjects with acquired immunodeficiency syndrome-related complex, and HIV-seropositive individuals with either lymphadenopathy only or no symptoms. Control subjects were HIV-seronegative heterosexuals and HIV-seronegative homosexuals. Two doses of inactivated influenza vaccine containing 15 micrograms of the hemagglutinin of influenza A/Taiwan/1/86(H1N1), A/Leningrad/360/86(H3N2), and B/Ann Arbor/1/86 were administered intramuscularly in the deltoid region 1 month apart. The second dose of vaccine did not significantly increase the frequency or magnitude of antibody responses of either HIV-seropositive or HIV-seronegative subjects over that achieved by a single dose. The two-dose regimen induced a protective level (greater than or equal to 1:64) of hemagglutination-inhibition antibody to influenza A(H1N1) or (H3N2) virus less often in subjects with symptomatic HIV infection than in uninfected control subjects (39% vs 87% or 46% vs 97%, respectively). Our results suggest that a substantial proportion of individuals with symptomatic HIV infection might remain unprotected from influenza, even after immunization with a two-dose regimen.