A Study to Evaluate the Shedding and Safety of Trivalent Influenza Virus Vaccine Live, Intranasal in Infants and Young Children

Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by polymerase chain reaction (PCR) based assays. Viral shedding (A/New Caledonia/20/99 [H1N1]; A/Wyoming/03/2003 [H3N2] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.

Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 [H1N1]; A/Wyoming/03/2003 [H3N2] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.

Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 [H1N1]; A/Wyoming/03/2003 [H3N2] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.

Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 [H1N1]; A/Wyoming/03/2003 [H3N2] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.

The number of days of shedding was summarized for all participants who shed any vaccine virus.

The number of days of shedding was summarized for all participants who shed confirmed A/H1N1 strain virus.

The number of days of shedding was summarized for all participants who shed confirmed A/H3N2 strain virus.

The number of days of shedding was summarized for all participants who shed confirmed B strain virus.

Quantitation of confirmed A/H1N1 shed vaccine virus was evaluated using the log transformed median tissue culture infectious dose (TCID50) per (/) millilitre (mL) for A/H1N1 vaccine strain and summarized for all participants who shed vaccine virus.

Quantitation of confirmed A/H3N2 shed vaccine virus was evaluated using the log (TCID50)/mL for A/H3N2 vaccine strain and summarized for all participants who shed vaccine virus.

Quantitation of confirmed B shed vaccine virus was evaluated using the log (TCID50)/mL for B vaccine strain and summarized for all participants who shed vaccine virus.

The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the cold-adapted (ca) and temperature-sensitive (ts) phenotypes. Viruses were considered ts if their titer at 39 degrees Celsius (°C) was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.

The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 39°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.

The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 37°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.

REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An SNMC is defined as a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. SNMCs included, but were not limited to, diabetes, asthma, autoimmune disease (lupus, rheumatoid arthritis), and neurological disease (epilepsy, autism).

REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability.