Is Reverse Vaccinology the Future?

The efficacy of a vaccine against an influenza strain is tested in the lab using the hemagglutinin inhibition (HI) assay. It has been a mainstay of the testing since the 1940s. The World Health Organization (WHO) uses it to validate the vaccines it recommends for a flu season. 

Developed in the early 1940s, HI is simple and inexpensive. The influenza virus has the hemagglutinin glycoprotein (HA) on its surface. It binds to the sialic acid on the cell surface to gain entry into the host cell. Since red blood cells (RBCs) have an abundance of sialic acid on their surface, the flu virus binds to the RBCs and agglutinates (i.e. clumps) them. This is the core strategy of the HI assay.

Twice a year, The Francis Crick Institute, London prepares an extensive report on influenza on behalf of WHO. The researchers at the Institute have concluded that “H3N2 viruses have become increasingly difficult to characterize by HI assay”. The report states that the HA assay is losing viability because H3N2 viruses are no longer agglutinating the RBCs effectively. Also, the results are becoming less repeatable.

WHO has started using other methods such as plaque reduction neutralization assay (PRNA) to supplement the HI assay. However, PRNA is difficult to conduct, prone to errors and expensive. Under the circumstances, alternates such as reverse vaccinology hold promise as the future of flu vaccine development and testing. 

Reverse vaccinology is the science of using genomic (DNA and RNA) data to identifying antigenic targets and designing vaccines. An antigenic target is what our immune system recognizes in a foreign entity such as a virus. The antigenic targets induce our immune system to develop protective antibodies. In the short term, reverse vaccinology or similar methods could supplement the traditional lab-based methods including HI and PRNA.

FutureFlu has developed Fourier-enhanced Phylogeny/Antigenicity Predictive Model (F^P/A-PM). It is a reverse vaccinology application for designing the flu vaccine from the genomic data. Some of the advantages of F^P/A-PM are

  • It increases the precision of measurement by fractionating the granular HI scale.
  • It can analyze an arbitrary mix of strains or even an entire clade such as a pandemic, which is not possible with an HI Assay.
  • It calculates the antigenicity of a strain from its sequence, without a wet lab, making it ideal for applications such as remote locations, poor locales and developing countries.
  • It has no associated cost.