Swine Influenza – An Attenuated Vaccine

Swine influenza virus (SIV) is a virus which has recently received widespread public attention due to a number of human casualties around the world, including some in Mexico, the United States, and Eastern Europe. Currently, vaccines against SIV are of the inactivated type and subsequently are not able to provide satisfactory immune response; moreover, as pigs are capable of contracting swine, human, and avian influenza, potential recombination of SIV into other mutant influenza strains are quite possible – a circumstance which would render current vaccines ineffective.

Researchers from the University of Saskatchewan, Canada, were able to develop a potential method of making attenuated SIV vaccine, by generating two separate mutant SIV strains that showed significantly lower rates of infection in swine host cells. To accomplish this, the researchers (Masic et al, 2009) modified the amino acid sequence encoded for the viral surface glycoprotein haemagglutinin (HA). HA is a glycoprotein vital for the virus’ pathogenicity, as it allows the virus to bind to host cell and enter the cytoplasm via receptor-mediated endocytosis; during SIV infection, HA is also the primary antigen against which host antibodies are produced. However, HA is not coded for directly by the virus; instead, the viral genetic material codes for an HA precursor, HA0, which is then cleaved by the host cell via the enzyme trypsin to form the active HA1 and HA2. If this process is not followed, the virus ceases to be infectious.

Masic et al (2009) were able to alter the 345th amino acid on the viral RNA coding for HA. Two mutant SIV strains were developed: one with a mutation from arginine to valine, and the other with a mutation from arginine to alanine. These mutations significantly hindered the virus’ ability to enter host cells; trypsin was unable to cleave the HA0 to HA1 and HA2. However, the modified mutants could only be cleaved by porcine pancreatic elastase; this meant that its survival and propagation was entirely elastase-dependent, hence possibly rendering the virus attenuated in human subjects.

The research conducted by Masic et al (2009) suggested the possibility of attenuated SIV vaccines. However, much future investigation is needed to ensure that modification of viral HA does not somehow have negative effects on the cells of a host.

Article:
Masic, A. et al. (2009) 'Reverse genetics-generated elastase-dependent swine influenza viruses are attenuated in pigs'. Journal of General Virology. Vol.90, pg.375-385.
Accessed from: EMBASE (Online) on 17th May, 2009.