Immunogenic and isotype‐specific responses to russian and US cold‐adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice

Abstract

The immunogenicity of the Russian cold-adapted (ca) donor stains, A/Leningrad (Len)/134/17/57 and A/Leningrad/134/47/57, and the US strain A/Ann Arbor (AA)/6/60-ca, were compared in BALB/c mice with their respective wild-type parental viruses. Each ca donor strain was less immunogenic than its wild-type parent. The vaccinating dose, when administered twice, which prevented multiplication of a standard challenge of parental wild-type virus in 50% of mice (the 50% protective dose or PD(50)), was shown for A/Len/134/17/57-ca, A/Len/134/47/57-ca, and A/AA/6/60-ca to be 10(3.77), 10(4.32), and 10(4.70), respectively. These findings were extended by measuring the number of antibody secreting cells induced in the lungs and mediastinal lymph nodes of mice infected with the same ca donors using an ELISPOT assay. When each donor strain was administered twice at a dose of 100 PD(50) over a 3-week interval, the overall immunoglobulin isotype antibody secreting cell profiles were shown to be similar. However, A/Len/134/17/57-ca and A/Len/134/47/57-ca induced significantly higher total immunoglobulin responses in the lungs than A/AA/6/60-ca (P < 0.05). A/Len/134/17/57-ca also induced a significantly greater IgA response in the lungs than A/AA/6/60-ca (P < 0.05). These results suggest that A/Len/134/17/57-ca is a superior immunogen to A/Len/134/47/57-ca which in turn is more immunogenic than A/AA/6/60-ca.

Development and Pre-Clinical Evaluation of Two LAIV Strains against Potentially Pandemic H2N2 Influenza Virus

“…As shown in Table 2, wild-type viruses easily infected the lower respiratory tract of mice and the MID 50 value did not exceed 1.0 log 10 , whereas 4.5 to 4.9 log 10 were required for cold-adapted viruses to infect 50% of the mice. These data are in concordance with previous findings about restriction of ca virus replication in mouse lung [20], [21].…”

“…Len/17 MDV was used for immunization in the 1960-s and was proven to be safe and immunogenic in children and adults [12], [46]. In addition, this strain was evaluated in animal models and was shown to be a superior immunogen compared to the more attenuated strain A/Leningrad/134/47/57 and caA/AA virus, on the basis of significantly higher IgG and IgA responses in mouse lung [20]. Moreover, in this study, we show that the Len/17 strain, which was included to assess the cross-protective effect of this well-characterized master donor virus induced (cross) reactive VN, HI and NI antibodies in ferrets and protected against heterologous challenge with A/Cal/66 and A/Tok/67.…”

Characterization of Reverse Genetics-Derived Cold-Adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants with H5N1 Surface Genes in a Mouse Model

“…Indeed, coldadapted caLen17-rg virus derived by reverse genetics is phenotypically equivalent to the parental caLen17 virus with regard to replication efficiency in the upper and lower respiratory tracts of mice, as the two viruses had similar high viral titers in nasal turbinates 3 dpi (3.4 to 3.6 log 10 ) and 6 dpi (2.5 to 2.8 log 10 ), whereas their replication in the lower respiratory tract was 30 to 300 times less efficient than that in the upper respiratory tract. These data further support previous findings about restricted pulmonary replication of cold-adapted viruses based on the caLen17 backbone in a mouse model (45,46), which is associated with the virus-attenuated phenotype.…”

“…In contrast to cold-adapted H2N2 viruses, wild-type Len134 virus was able to replicate in mouse lung to high titers (5.1 log 10 at 3 dpi), which correlates with previous studies (45) showing that mice inoculated i.n. with wt Len134 had ϳ4.5 log 10 50% egg infective doses (EID 50 ) in lungs at 3 dpi, whereas the caLen17 virus was below detection levels.…”

Safety, immunogenicity and infectivity of new live attenuated influenza vaccines

“…Of note, an animal side-by-side study revealed more attenuated phenotype of the A/AA MDV, compared with Len/ 17 [48]. Unfortunately, all the clinically tested pandemic LAIVs had different sources of HA and neuraminidase (NA) genes, and it was not possible to determine the impact of the attenuated backbone on vaccine virus infectivity.…”