Development of cold-adapted recombinant live, attenuated influenza A vaccines in the U.S.A. and U.S.S.R.

Kendal, Alan P.; Maassab, Hunein F.; Alexandrova, Galina I.; Ghendon, Y. Z.

doi:10.1016/0166-3542(82)90034-1

Cited by 79 publications

(27 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The vaccination at present is accomplished with the commercially available chemically inactivated (killed) or live coldadapted (ca) attenuated influenza virus vaccines (10,28,36). The vaccine efficacy for both types of vaccines has been reported to be comparable in adults.…”

mentioning

confidence: 99%

Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes

Ferko

Stasakova

Romanova

et al. 2004

J Virol

106

100

View full text Add to dashboard Cite

We explored the immunogenic properties of influenza A viruses with altered NS1 genes (NS1 mutant viruses). NS1 mutant viruses expressing NS1 proteins with an impaired RNA-binding function or insertion of a longer foreign sequence did not replicate in murine lungs but still were capable of inducing a Th1-type immune response resulting in significant titers of virus-specific serum and mucosal immunoglobulin G2 (IgG2) and IgA, but with lower titers of IgG1. In contrast, replicating viruses elicited high titers of serum and mucosal IgG1 but less serum IgA. Replication-deficient NS1 mutant viruses induced a rapid local release of proinflammatory cytokines such as interleukin-1␤ (IL-1␤) and IL-6. Moreover, these viruses also elicited markedly higher levels of IFN-␣/␤ in serum than the wild-type virus. Comparable numbers of virus-specific primary CD8؉ T cells were determined in all of the groups of immunized mice. The most rapid onset of the recall CD8؉ -T-cell response upon the wild-type virus challenge was detected in mice primed with NS1 mutant viruses eliciting high levels of cytokines. It is noteworthy that there was one NS1 mutant virus encoding NS1 protein with a deletion of 40 amino acids predominantly in the RNA-binding domain that induced the highest levels of IFN-␣/␤, IL-6 and IL-1␤ after infection. Mice that were immunized with this virus were completely protected from the challenge infection. These findings indicate that a targeted modification of the RNA-binding domain of the NS1 protein is a valuable technique to generate replication-deficient, but immunogenic influenza virus vaccines.Human influenza, caused by influenza A and B viruses, is a highly infectious acute respiratory disease spreading around the world in seasonal epidemics resulting in high morbidity and significant mortality. Influenza viruses have a segmented negative-strand RNA genome that encodes 10 or 11 proteins depending on the strain. The exchange of individual genome segments between different virus subtypes during a mixed infection (genetic reassortment) and the relatively rapid accumulation of point mutations in virus surface glycoproteins due to the high mutation rate of the RNA genome are the main reasons for antigenic "shift" and "drift" variations of emerging viruses escaping the preexisting immunity of the human population (53-55). Attempts to develop a vaccine inducing a longlasting protection against influenza have thus far been unsuccessful. In order to protect humans against circulating epidemic influenza virus strains, vaccine producers have to generate vaccines containing actualized influenza A (H1N1 and H3N2) and B virus components almost annually (19).The vaccination at present is accomplished with the commercially available chemically inactivated (killed) or live coldadapted (ca) attenuated influenza virus vaccines (10, 28, 36). The vaccine efficacy for both types of vaccines has been reported to be comparable in adults. However, live vaccines, apart from the easy and painless nasal administration induce not only the h...

show abstract

mentioning

confidence: 99%

Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes

Ferko

Stasakova

Romanova

et al. 2004

J Virol

106

100

View full text Add to dashboard Cite

show abstract

“…Annual human influenza epidemics (caused by influenza type A or type B viruses) are manifested as highly infectious acute respiratory disease with high morbidity and significant mortality. Vaccination is accomplished at present with commercially available, chemically inactivated (killed) or live attenuated influenza virus vaccines (10,31,48).…”

mentioning

confidence: 99%

Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts

Ferko

Kittel

Romanova

et al. 2006

J Virol

View full text Add to dashboard Cite

Despite the reported efficacy of commercially available influenza virus vaccines, a considerable proportion of the human population does not respond well to vaccination. In an attempt to improve the immunogenicity of live influenza vaccines, an attenuated, cold-adapted (ca) influenza A virus expressing human interleukin-2 (IL-2) from the NS gene was generated. Intranasal immunization of young adult and aged mice with the IL-2-expressing virus resulted in markedly enhanced mucosal and cellular immune responses compared to those of mice immunized with the nonrecombinant ca parent strain. Interestingly, the mucosal immunoglobulin A (IgA) and CD8؉ T-cell responses in the respiratory compartment could be restored in aged mice primed with the IL-2-expressing virus to magnitudes similar to those in young adult mice. The immunomodulating effect of locally expressed IL-2 also gave rise to a systemic CD8 ؉ T-cell and distant urogenital IgA response in young adult mice, but this effect was less distinct in aged mice. Importantly, only mice immunized with the recombinant IL-2 virus were completely protected from a pathogenic wild-type virus challenge and revealed a stronger onset of virus-specific CD8 ؉ T-cell recall response. Our findings emphasize the potential of reverse genetics to improve the efficacy of live influenza vaccines, thus rendering them more suitable for high-risk age groups.

show abstract

“…The A/Leningrad/134/47/57 (H2N2) strain (A/Len/47) was obtained by 47 sequential passages of the A/Leningrad/134/57 wild-type virus (A/Len/wt) in fertile hens' eggs (CE) at 25 °C. This ca and highly attenuated master strain is used to prepare live reassortant vaccines of the A(H1N1) and A(H3N2) subtypes for immunization of children Ghendon et al, 1984;Kendal et al, 1981). These reassortant vaccines are non-reactogenic and immunogenic for children 3-15 years old when used as monovalent (Kendal et al, 1981), bivalent (H1NI+H3N2) (Alexandrova et al, , 1986Ghendon et al, 1984) or trivalent (H1N1 + H3N2 + type B) preparations (Rudenko et al, 1993).…”

mentioning

confidence: 99%

Genetic stability of cold-adapted A/Leningrad/134/47/57 (H2N2) influenza virus: sequence analysis of live cold-adapted reassortant vaccine strains before and after replication in children

Klimov

Egorov

Gushchina

et al. 1995

Journal of General Virology

View full text Add to dashboard Cite

We previously reported that the A/Leningrad/134/47/57 (H2N2) cold-adapted virus (A/Len/47) used in preparing reassortant live attenuated vaccines for children acquired 14 (11 coding) mutations in genes coding for proteins other than haemagglutinin and neuraminidase during cold-adaptation. Preservation of these mutations in genomes of viruses isolated from children on the second, fifth, or eighth day after vaccination was examined by sequence analysis. The sequence data demonstrated that all nine coding mutations selected for examination were conserved in the genomes of all 11 strains investigated, indicating that the mutations accompanying cold-adaptation and attenuation of the A/Len/47 master vaccine are highly stable.

show abstract

Development of cold-adapted recombinant live, attenuated influenza A vaccines in the U.S.A. and U.S.S.R.

Cited by 79 publications

References 46 publications

Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes

Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes

Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts

Genetic stability of cold-adapted A/Leningrad/134/47/57 (H2N2) influenza virus: sequence analysis of live cold-adapted reassortant vaccine strains before and after replication in children

Contact Info

Product

Resources

About