TY - JOUR
T1 - Induction of humoral and cellular immunity against influenza virus by immunization of newborn mice with a plasmid bearing a hemagglutinin gene
AU - Bot, Adrian
AU - Antohi, Stephan
AU - Bot, Simona
AU - Garcia-Sastre, Adolfo
AU - Bona, Constantin
PY - 1997
Y1 - 1997
N2 - Neonates and infants display an intrinsic disability to mount protective immune responses to influenza viruses or conventional influenza vaccines. We investigated the ability of naked DNA to prime protective immune responses by inoculating newborn and adult mice with a plasmid (pHA) expressing hemagglutinin (HA) from the neurovirulent strain A/WSN/33 of influenza virus. Continuous exposure to small doses of antigen subsequent to neonatal DNA immunization led to effective priming of specific B and T(h) cells, rather than tolerance induction. The pHA immunization of adult mice primed a strongly biased T(h)1 response, whereas in neonates it induced a mixed T(h)1/T(h)2 response. In contrast to the effect of live-virus immunization, DNA immunization of neonates was followed by enhanced cytotoxic T lymphocyte responses subsequent to challenge with A/WSN/33 influenza virus. Mice immunized as neonates or adults with pHA plasmid exhibited significant increases in survival and decreases in virus lung titers following lethal challenge with the A/WSN/33 virus or the A/PR8/34 drift variant. Our results demonstrate that DNA vaccination is an efficient and safe means to generate broad humoral and cellular immune responses to influenza viruses, during the earliest stages of postnatal life.
AB - Neonates and infants display an intrinsic disability to mount protective immune responses to influenza viruses or conventional influenza vaccines. We investigated the ability of naked DNA to prime protective immune responses by inoculating newborn and adult mice with a plasmid (pHA) expressing hemagglutinin (HA) from the neurovirulent strain A/WSN/33 of influenza virus. Continuous exposure to small doses of antigen subsequent to neonatal DNA immunization led to effective priming of specific B and T(h) cells, rather than tolerance induction. The pHA immunization of adult mice primed a strongly biased T(h)1 response, whereas in neonates it induced a mixed T(h)1/T(h)2 response. In contrast to the effect of live-virus immunization, DNA immunization of neonates was followed by enhanced cytotoxic T lymphocyte responses subsequent to challenge with A/WSN/33 influenza virus. Mice immunized as neonates or adults with pHA plasmid exhibited significant increases in survival and decreases in virus lung titers following lethal challenge with the A/WSN/33 virus or the A/PR8/34 drift variant. Our results demonstrate that DNA vaccination is an efficient and safe means to generate broad humoral and cellular immune responses to influenza viruses, during the earliest stages of postnatal life.
KW - DNA vaccination
KW - Neonatal immunization
KW - T(h)1
KW - T(h)2
UR - http://www.scopus.com/inward/record.url?scp=0030734521&partnerID=8YFLogxK
U2 - 10.1093/intimm/9.11.1641
DO - 10.1093/intimm/9.11.1641
M3 - Article
C2 - 9418125
AN - SCOPUS:0030734521
SN - 0953-8178
VL - 9
SP - 1641
EP - 1650
JO - International Immunology
JF - International Immunology
IS - 11
ER -