Pediatr Allergy Respir Dis.  2001 Jun;11(2):80-92.

Protection Against Respiratory Syncytial Virus Infection Induced Airway Hyperresponsiveness by DNA Encoding RSV-G Protein Immunization

• Cho JY
• Lim DH
• Baek KJ
• In KH
• Yoo SH
• Broide DH

Abstract

PURPOSE
Respiratory syncytial virus is the primary cause of pneumonia and bronchiloitis in young children and infants. RSV infection is also known to be very important to asthma patient, because previous RSV infection increases the frequency of the asthma development and RSV infection may cause airway hyperresponsiveness. Natural RSV infection does not provide complete immunity and reinfection occurs throughout life. Several strategies have recently been used in RSV vaccine development, including the generation of formalin inactivated RSV(FI-RSV), peptides, recombinant vaccine viruses (rVV), and DNA based vaccines. Previous studies in mice primed with RSV G protein enhanced lung pathology resulted from a Th2 host immune response against the viral G protein. We studied for the evaluation of protective immunity, effect on airway hyperesponsiveness, and influence on lung pathology after pND G immunization.
METHODS
BALB/c mice were injected with pND G(50g in 1 g/l PBS), pND G-HA (50 g), pND(50 g) FI-RSV(10 6PFU) i.d.at 0, 2, 4 weeks. Four weeks later, mice were challenged with RSV(10 6PFU). Mice were sacrificed on postchallenge day 4 and their lungs were removed for RT-PCR and viral titration. The other mice were sacrificed on postchallenge day 6 for bronchoalveolar lavage, serum and histologic examination. Airway responsiveness was assessed by using a single chamber whole body plethysmography on post challenge day 5.
RESULTS
1) Vaccination with pND-G reduced the Mch(methacholine) induced airway hyperresponsiveness after RSV infection(P<0.05). 2) Viral titers are decreased in pND-G group and FI-RSV group(P<0.05) and complete protection from RSV infection was 9/12(75%) in pND-G group. 3) Serum anti-G IgG antibody is more increased in pND-G group than RSV group(P<0.05). 4) IFN-/IL-5 ratio is increased in pND-G group(0.59) and decreased in FI-RSV group(P<0.036). 5) Inflammatory response in BAL after RSV infection was decreased by pND-G vaccination(P>0.05).
CONCLUSION
In this study, immunization with pND encoding G protein induced decrease in airway hyperresponsiveness, and protection against RSV infection of the lower respiratory tract infection and also induced virus neutralizing antibody and decrease in lymphocytic inflammation. pND G immunization elicited balanced pulmonary Th1/Th2 cytokine response without atypical pulmonary inflammatory responses.

Keyword

Respiratory syncytial virus; RSV G protein; DNA vaccine; Airway hyperresponsiveness

MeSH Terms

Animals
Antibodies, Neutralizing
Asthma
Bronchoalveolar Lavage
Child
DNA*
Formaldehyde
GTP-Binding Proteins
Humans
Immunization*
Immunoglobulin G
Infant
Inflammation
Lung
Mice
Pathology
Peptides
Plethysmography, Whole Body
Pneumonia
Respiratory Syncytial Viruses*
Respiratory Tract Infections
Vaccination
Vaccines
Antibodies, Neutralizing
DNA
Formaldehyde
GTP-Binding Proteins
Immunoglobulin G
Peptides
Vaccines