Protective efficacy of intranasal cold-adapted influenza A/New Caledonia/20/99 (H1N1) vaccines comprised of egg- or cell culture-derived reassortants.
Live, cold-adapted, temperature-sensitive (ca/ts) Russian influenza A vaccines are prepared in eggs by a 6:2 gene reassortment of the ca/ts donor strain A/Leningrad/134/17/57 (H2N2) (Len/17) with a current wild-type (wt) influenza A strain contributing hemagglutinin (HA) and neuraminidase (NA) genes. However, egg-derived reassortant vaccines are potentially more problematic to manufacture in large quantities than vaccines from cell-based procedures. To compare egg- and cell culture-derived reassortant vaccines, we prepared in Madin Darby canine kidney (MDCK) cells two cloned, ca/ts reassortants (25M/1, 39E/2) derived from Len/17 and a wt reference strain A/New Caledonia/20/99 (H1N1) (NC/wt). Both 25M/1 and 39E/2 reassortants preserved the ca/ts phenotype and mutations described for internal genes of the A/Len/17 parent. When compared to a commercial, egg-derived ca/ts Russian A/17/NC/99/145 (H1N1) New Caledonia vaccine (NC/145), the MDCK-derived reassortant 39E/2 vaccine conferred similar levels of protection in ferrets challenged i.n. with 7 x 10(10) pfu of NC/wt. In a dose-ranging study, the protective vaccine dose for 50% of ferrets (PD50) was less than 1.2 x 10(4) pfu for the 25M/1 vaccine derived by recombination and amplification in MDCK cells. Clonal isolates of ca/ts influenza A/New Caledonia/20/99 (H1N1) obtained by recombination and amplification entirely in MDCK cells can be highly protective i.n. vaccines.
Palker
Thomas
T
Department of Virus and Cell Biology, Vaccine and Biologics Research, Merck Research Laboratories, Merck and Co., Inc., 770 Sumneytown Pike, WP16-101, West Point, PA 19486, USA. tom_palker@merck.com
Kiseleva
Irina
I
Johnston
Kimberly
K
Su
Qin
Q
Toner
Timothy
T
Szymkowiak
Christopher
C
Kwan
Wan-Sang
WS
Rubin
Boris
B
Petrukhin
Luba
L
Wlochowski
Joan
J
Monteiro
Juanita
J
Kraiouchkine
Nikolai
N
DiStefano
Daniel
D
Rudenko
Larisa
L
Shaw
Alan
A
Youil
Rima
R
D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002460:Cell Line; D002642:Chick Embryo; D004195:Disease Models, Animal; D004285:Dogs; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D017817:Nasal Lavage Fluid / Q000821:virology; D009439:Neuraminidase / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016865:Reassortant Viruses / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D014611:Vaccination; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014764:Viral Proteins; D009439:Neuraminidase