Investigation of a Trimeric Hemagglutinin Stem Domain from Influenza B for a Universal Vaccine

Abstract

Influenza infection occurs in as much as 5–15% of the world population, resulting in 3–5 million cases of severe illness and up to 500,000 deaths annually. According to the CDC, on average 24% of all influenza positive respiratory samples during 2001 to 2011 tested positive for Influenza B. Influenza has two main surface glycoproteins, neuraminidase (NA) and hemagglutinin (HA), HA being responsible for the binding of the virus to the host cell. Currently, seasonal influenza vaccines are produced using two strains of Influenza A and one or two strains of Influenza B viruses recommended by the World Health Organization (WHO). These vaccines are mainly targeting the head domain of the HA protein, which mutates constantly, hence the need for annual vaccine updates. The goal of this research is to develop an experimental universal vaccine against influenza B and increase our knowledge to help pave the way for finding a one-time vaccination alternative, reducing the need for a yearly flu shot. To achieve the above, protection and toxicity studies were conducted in DBA/2 mice immunized with a designed HA2 adenoviral-vectored vaccine targeting the HA stem region of influenza B. Results showed that this designed vaccine was able to confer 100% survival protection, this was supported by lower viral titer in trachea and lung tissues. Additionally, we studied the influence of CD40L as a targeting adjuvant, by analyzing its effect on the humoral and cellular immune response, where results showed that it has a significant effect by inducing a higher TH1-bias response. This research is the first report that leads us to a better understanding of the potential use of a conserved consensus HA2 sequence to induce protection against influenza B virus.