Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine Recipients.

Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.

Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults.

Background: High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination.

Correlates of Protection against Influenza in the Elderly: Results from an Influenza Vaccine Efficacy Trial.

Although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. A recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired A/H3N2 influenza illness. The high-dose vaccine induced significantly higher antibody titers than the standard-dose vaccine for all assays.

Some extensions in continuous models for immunological correlates of protection.

Background: A scaled logit model has previously been proposed to quantify the relationship between an immunological assay and protection from disease, and has been applied in a number of settings. The probability of disease was modelled as a function of the probability of exposure, which was assumed to be fixed, and of protection, which was assumed to increase smoothly with the value of the assay.

Methods: Some extensions are here investigated.

Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines.

Background: A recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection.

Efficacy and immunogenicity of high-dose influenza vaccine in older adults by age, comorbidities, and frailty.

Background: A randomized trial demonstrated that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose vaccine (IIV-SD) against laboratory-confirmed influenza illness in adults ≥65 years. To evaluate the consistency of IIV-HD benefits, supplemental analyses explored efficacy and immunogenicity by baseline characteristics of special interest.

Control of type 1 error in a hybrid complete two-period vaccine efficacy trial.

A complete two-period experimental design has been defined as one in which subjects are randomized to treatment, observed for the occurrence of an event of interest, re-randomized, and observed again for the event in a second period. A 4-year vaccine efficacy trial was planned to compare a high-dose vaccine with a standard dose vaccine. Subjects would be randomized each year, and subjects who had participated in a previous year would be allowed to re-enroll in a subsequent year and would be re-randomized.

Efficacy of high-dose versus standard-dose influenza vaccine in older adults.

Background: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness.

Methods: We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older.

A threshold method for immunological correlates of protection.

Background: Immunological correlates of protection are biological markers such as disease-specific antibodies which correlate with protection against disease and which are measurable with immunological assays. It is common in vaccine research and in setting immunization policy to rely on threshold values for the correlate where the accepted threshold differentiates between individuals who are considered to be protected against disease and those who are susceptible. Examples where thresholds are used include development of a new generation 13-valent pneumococcal conjugate vaccine which was required in clinical trials to meet accepted thresholds for the older 7-valent vaccine, and public health decision making on vaccination policy based on long-term maintenance of protective thresholds for Hepatitis A, rubella, measles, Japanese encephalitis and others.

High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season.

Background: High-dose trivalent influenza vaccine was developed to improve antibody responses to influenza vaccine in the elderly and hence potentially impact favorably on influenza-associated morbidity and mortality in this population.

Methods: A phase IIIb, multicenter, randomized, double-blind, controlled trial was conducted to compare High-Dose (HD) trivalent inactivated influenza vaccine (60μg of hemagglutinin [HA] per strain) to standard dose (SD) vaccine (15μg of HA per strain) in adults ≥65 years of age. Assessments of safety (serious adverse events [SAE]), immunogenicity (hemagglutination inhibition [HAI] titers) and relative efficacy were performed during the 2009-2010 influenza season, which coincided with the H1N1 pandemic.

Efficacy and safety of a live attenuated influenza vaccine in adults 60 years of age and older.

This randomized, double-blind, placebo-controlled study investigated the efficacy, safety, and immunogenicity of LAIV in community-dwelling ambulatory adults > or =60 years of age in South Africa in 2001. Nose and throat swabs were obtained for influenza virus culture based on the symptoms of influenza-like illness. A total of 3242 subjects were enrolled, with a mean age of 69.

Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children.

The highly sensitive gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot (ELISPOT) assay permits the investigation of the role of cell-mediated immunity (CMI) in the protection of young children against influenza. Preliminary studies of young children confirmed that the IFN-gamma ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to <36 months, an intranasal dose of 10(7) fluorescent focus units (FFU) of a live attenuated influenza virus vaccine (CAIV-T) elicited substantial CMI responses. A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination.

A model for immunological correlates of protection.

Immunological assays measure characteristics of the immune system, such as antibody levels, specific to certain diseases. High assay values are often associated with protection from disease. A question of interest is how the relationship between assay values and subsequent development of disease should be quantitatively modelled.