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Evaluate Reactogenicity & Immunogenicity of an Influenza Pandemic Candidate Vaccine (GSK1562902A) in Primed Adults

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00506350
First Posted: July 25, 2007
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The present study is designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine. Fifty new subjects who did not participate in a primary study (106750, NCT00309634) will be recruited. This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00309634)

Condition Intervention Phase
Influenza Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluate the Reactogenicity & Immunogenicity of 1 or 2 Booster Administrations of an Influenza Pandemic Candidate Vaccine (GSK1562902A) in Primed Adults Aged Between 19 & 61 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Titers for Serum H5N1 Haemagglutinin Inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 0 ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005.

  • Titers for Serum H5N1 Haemagglutinin Inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 21 ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005.

  • Number of Seroconverted Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 21 ]
    Seroconversion rate for HI antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer.

  • Seroconversion Factor (SCF) for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 21 ]
    Seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strain assessed was A/Indonesia/05/2005.

  • Number of Seroprotected Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 0 ]
    A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was A/Indonesia/05/2005.

  • Number of Seroprotected Subjects for H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Day 21 ]
    A seroprotected subject was defined as a vaccinated subject with a serum HI titer equal to or above (≥) 1:40. The flu strain assessed was A/Indonesia/05/2005.

  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]
    Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. No subject from GSK1562902A AD F1 Primed Group has received Dose 2.

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]
    Assessed solicited general symptoms were arthralgia, fatigue, headache, myalgia, shivering, sweating and fever [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination. No subject from GSK1562902A AD F1 Primed Group has received Dose 2.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 21-day (Days 0-20) follow-up period after the first vaccination and 30-day (Days 0-29) follow-up period after the second vaccination ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day (Days 0-29) follow-up period after the first vaccination ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (From Day 0 up to Month 24) ]
    SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.


Secondary Outcome Measures:
  • Titers for Serum Neutralizing HI Antibodies Against A/Indonesia/05/2005 Strain [ Time Frame: At Days 0, 21 (post-vaccination one) and 42 (post-vaccination two) ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strain assessed was A/Indonesia/05/2005. No subject from GSK1562902A AD F1 Primed Group has received a second vaccination.

  • Titers for Serum Neutralizing HI Antibodies Against A/Indonesia/05/2005 Stain [ Time Frame: At Months 6, 12, 18 and 24 ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:28. The flu strain assessed was A/Indonesia/05/2005.

  • Titers for Serum H5N1 Haemaglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Days 0, 7, 14, 21, 28, 35 and 42 ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005.

  • Titers for Serum H5N1 HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Months 6, 12, 18 and 24 ]
    Titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was equal to or above (≥) 1:10. The flu strain assessed was A/Indonesia/05/2005.

  • Number of Seroconverted (SCR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Days 7,14, 21, 35 and 42 ]
    Seroconversion (SCR) was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer < 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.

  • Number of Seroconverted (SCR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Months 6, 12, 18 and 24 ]
    SCR was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer< 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-vaccination reciprocal titer against the vaccine virus. The flu strain assessed was Flu A/Indonesia/05/2005.

  • Number of Seroconverted (SCR) Subjects for Neutralizing HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Days 21 (post-vaccination one) and 42 (post-vaccination two) ]
    Seroconversion rate for anti-HA antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:56 and at least a 4-fold increase in post-vaccination titer.

  • Number of Seroconverted (SCR) Subjects for Neutralizing HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Months 6, 12, 18 and 24 ]
    Seroconversion rate for neutralizing antibody response was defined as the percentage of vaccines who have either a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:56 and at least a 4-fold increase in post-vaccination titer.

  • Seroconversion Factor (SCF) for H5N1 Haemagglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Days 7, 14, 21, 35 and 42 ]
    Seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strain assessed was A/Indonesia/05/2005.

  • Seroconversion Factor (SCF) for H5N1 Haemagglutinin-inhibition (HI) Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Months 6, 12, 18 and 24 ]
    Seroconversion factor (SCF) was defined as the fold increase in H5N1 HI antibody GMTs post-vaccination compared to Day 0. The flu strains assessed were A/Indonesia/05/2005.

  • Number of Seroprotected (SPR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Days 0, 7, 14, 21, 28, 35 and 42 ]

    Seroprotection rate was defined as the percentage of vaccines with a serum HI antibody titer ≥ 1:40 that usually is accepted as indicating protection.

    The flu strain assessed was A/Indonesia/05/2005 (H5N1).


  • Number of Seroprotected (SPR) Subjects for HI Antibodies Against the A/Indonesia/05/2005 Strain [ Time Frame: At Months 6, 12, 18 and 24 ]
    Seroprotection rate was defined as the percentage of vaccines with a serum HI antibody titer ≥ 1:40 that usually is accepted as indicating protection. The flu strain assessed was A/Indonesia/05/2005 (H5N1).

  • Frequency of Antigen-specific CD4/CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines [ Time Frame: At Days 0 and 21 ]
    Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The flu strains assessed wwere H5N1 A/Indonesia and H5N1 A/Vietnam.

  • Frequency of Antigen-specific CD4/CD8 T-cells (Per 10E6) in Tests Identified as Producing at Least Two Out of Four Different Cytokines [ Time Frame: At Months 6, 12, 18 and 24 ]
    Among cytokines expressed after background reduction were cluster of differentiation 4 all doubles (CD4 all doubles), cluster of differentiation 40-ligand (CD40-L), interleukin-2 (IL-2), interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The flu strains assessed were H5N1 A/Indonesia and H5N1 A/Vietnam.


Enrollment: 350
Actual Study Start Date: August 1, 2007
Study Completion Date: October 12, 2009
Primary Completion Date: October 12, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK1562902A non-AD F1 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 1 (F1) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated intramuscularly (IM) in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses
Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.
Experimental: GSK1562902A non-AD F2 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 2 (F2) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses
Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.
Experimental: GSK1562902A non-AD F3 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 3 (F3) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses
Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.
Experimental: GSK1562902A non-AD F4 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of a non-adjuvanted (non-AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 4 (F4) in study 106750 (NCT00309634) receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses
Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.
Experimental: GSK1562902A AD F1 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation1 (F1) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose
A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.
Experimental: GSK1562902A AD F2 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 2 (F2) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose
A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.
Experimental: GSK1562902A AD F3 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of an adjuvanted (AD) investigational H5N1 vaccine (A/Vietnam/1194/04 strain) Formulation 3 (F3)in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose
A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.
Experimental: GSK1562902A AD Approved F4 Primed Group
Healthy male or female adults, between and including 19 to 61 years of age, primed with 2 doses of approved Formulation (F) of adjuvanted (AD) H5N1 vaccine (A/Vietnam/1194/04 strain) in study 106750 (NCT00309634) received 1 dose of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study at Day 0, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 1 dose
A single dose of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0.
Experimental: Control Group
Healthy male or female adults, between and including 19 to 61 years of age, unprimed receiving 2 doses of Pandemic influenza candidate vaccine (GSK1562902A) in this booster study, one at Day 0 and one at Day 21, administrated IM in the deltoid region of the non-dominant arm.
Biological: Pandemic influenza candidate vaccine (GSK1562902A) - 2 doses
Two doses of Pandemic influenza candidate vaccine (GSK1562902A) administered intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21.

Detailed Description:
The present study is designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine. The persistence of antibodies will be analysed at 6, 12, 18 and 24 months.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years to 61 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study.
  • For previously primed subjects: participation in the primary study (NCT00309634).
  • For unprimed subjects: male or female between and including, 19 and 61 years of age at the time of the first vaccination.
  • Written informed consent obtained from the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • For unprimed subjects who did not participate in the primary study (NCT00309634): Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
  • Planned administration/ administration of a licenced vaccine not foreseen by the study protocol within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) of the first dose of vaccine(s).
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
  • Applicable for control group only: previous vaccination with a pandemic candidate vaccine or a vaccine containing the investigational vaccine adjuvant.
  • History of hypersensitivity to vaccines.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
  • Major congenital defects or serious chronic illness.
  • History of any neurological disorders or seizures.
  • Acute disease at the time of enrolment.
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
  • Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
  • Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.
  • Lactating female.
  • History of chronic alcohol consumption and/or drug abuse
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00506350


Locations
Belgium
GSK Investigational Site
Gent, Belgium, 9000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 109817
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00506350     History of Changes
Other Study ID Numbers: 109817
First Submitted: July 24, 2007
First Posted: July 25, 2007
Results First Submitted: September 11, 2017
Results First Posted: October 4, 2017
Last Update Posted: October 4, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs