Orthomyxoviridae
Orthomyxoviridae is characterized by 18 HA subtypes, according to recent study.
Influenza Season
Infections caused by the H1N1 virus lead to between 250,000 and 500,000 fatalities globally. In the majority of influenza A virus outbreaks, viral RNA segments result in new strains that are vulnerable to human immunity. Such occurrences can be linked to the severe outbreak of 2009. Due to the regular "point mutations in the antigenic epitopes of HA" (Robertson et al. 1837), customarily referred to as the Antigenic Drift, and the introduction of HA to which human organisms are vulnerable, the WHO recommends to get periodically (1 to 5 years) administered with the new influenza A vaccines.
Hypothesis and Experiments
The process of "generation of inactivated vaccines" requires the use of the NA and HA in the RNA viral segments, which are characteristically combined with the residual "six viral RNA segments of A/Puerto Rico/8/34 (PR8; H1N1) virus" (Robertson et al. 1838). The results are achieved through the application of reverse genetics or re-assortment approaches. The development of influenza A vaccine virus entails the procedure "propagated in embryonated chicken eggs." Another perspective favored by researchers is the "Mammalian cell culture-based vaccine production" (Robertson et al. 1838). The latter method has a preference of the egg-based system grounded on its ability to be scaled up and the significant reduction in the risks mutations, emerging as a consequence of antigenic changes. One more approach identified by scientists to boost vaccine production is the modification of the PR8 virus backbone, through this means the efficiency of the replication rate can be raised. Comprehensive studies have been developed in line with the PR8 vaccine backbone with the aim of obtaining the vaccine virus that produces several "seasonal pandemic influenza vaccine strains in cell culture."
The Results
At present, there is little information from the experiments conducted to assist in understanding which mutations associated with PR8 have a higher virus replicative capacity in cultured cells. The process entailed using a high-throughput mutagenesis technique plus a screening approach with the aim of identifying mutations that are associated with "high yield of PR8" (Robertson et al. 1839). In detailed experimentation, error-prone PCR was employed to generate broad sets of viral cDNAs that portray elements of random modifications. In the application of reverse genetics or re-assortment, mutant sets (libraries) are used which in turn leads to the production of virus libraries composed of numerous variants having "random amino-acid in either one or myriad viral proteins" (Robertson et al. 1840).
Strengths and Weaknesses of the Vaccine Virus Work
Like every other scientific research, the exercise is associated with some drawbacks and breakthroughs. The widely used "embryonated chicken eggs" influenza vaccine production system reveals several faults (Robertson et al.). One of these is the possible limitations in egg supply in case of an outbreak of the influenza A virus when there is an immediate need for large-scale production of vaccines. Second, virus propagations associated with "embryonated chicken eggs" often culminates in "eggs-adapting mutations" regarding HA, which as a crucial factor associated with the antigenicity of the virus and is the leading cause in reduced "efficacy of some influenza vaccines" (Robertson et al. 1840). The major advantage associated with mammalian cell culture system is that the absence of egg proteins in the process due to the cell culture-based vaccines eradicates the possibility of complications for persons with egg allergies.
Work Cited
Robertson, James S., et al. “The development of vaccine viruses against pandemic A (H1N1) influenza.” Vaccine, vol. 29, no. 9, 2011, pp. 1836–1843.
