Shedding, Immunogenicity and Safety of Quadrivalent Live Intranasal Influenza Vaccine (QLAIV) in HIV-infected Children and Young Adults

QLAIV is an intranasal vaccine that works by using 4 different attenuated strains of
influenza virus that will replicate in the nose and stimulate an immune response in
recipients that should protect them if they are infected with one of those strains of
influenza in the future. A couple of studies have shown an increase in duration that the
viruses remain in the nose in immunocompromised people. Those studies were done using the
trivalent vaccine, so the investigators would like to evaluate the quadrivalent vaccine, and
there is still a need for additional data to help understand the duration of shedding. If
shedding is prolonged in HIV-infected children and young adults, it would be important to
know for contacts of those individuals who are very immunocompromised. Shedding will be
measured by looking for influenza RNA in nasopharyngeal swabs taken at baseline, 2-5 days,
7-10 days and 14-21 days after the intranasal immunization.

The live-attenuated influenza vaccines have been shown to have increased effectiveness in
children and they stimulate the immune system in a different way than the inactivated
influenza vaccines (TIV or QIV). In this study, the investigators will have the opportunity
to compare the immunogenicity of QLAIV, measured at baseline and 14-21 days post-vaccination,
in HIV-infected and uninfected children, adolescents and young adults. Although prior studies
of LAIV in HIV-infected and other immunocompromised children and adults have not shown any
increase in serious adverse events, safety will be actively monitored for the first 30-45
days through a study-specific questionnaire administered at each clinic or phone visit and by
asking the subjects to keep a diary of side effects. Safety will be monitored passively
throughout the course of the study.

Inclusion Criteria:

- Age 2-25

- Only supposed to get one dose of vaccine for upcoming influenza season

- No viral respiratory symptoms at time of immunization

- HIV-infected group: must have:

- HIV-infection documented by 2 tests such as positive serology, positive HIV DNA
or positive HIV RNA;

- must thave a CD4>25% or 500, or

- must have CD4>15% or 200 and be on HAART

- Healthy controls: no major medical problems affecting the immune system

- Recruited among:

- HIV-unifected clients of the Children's Immunodeficiency Program(CHIP),

- Children's Hospital Colorado Child Health Clinic and Adolescent Clinics.

Exclusion Criteria:

- History of:

- reactive airway disease,

- recurrent wheezing, or

- asthma

- Active wheezing at time of immunization

- On any antiviral agents active against influenza (amantadien/rimantadine, zanamavir,
oseltamivir) at time of immunization or planned over 21 days of shedding collection

- Receipt of IVIG within 3 months prior to enrollment

- Plan to receive IVIG during the 4 weeks after immunization

- Moderate to severely immunocompromised individual living in the home

- Pregnant

- Breastfeeding

- Plan to start immunosupressive medications or stop HAART over the 4 weeks following
immmunization

- Temperature > 100F or 37.8C

- Rhinorrhea or cough not related to allergies at the time of immunization

- History of fungal sinusitis

- History of Guillain-Barre Syndrome

- Current on antibiotics

- Currently taking aspirin

- On an investigational drug at the time of immunization or planned over the 28 days of
shedding collection

- On any experimental medication at time of immunization or planned over 21 days of
shedding collection