Towards a universal influenza vaccine: different approaches for one goal

Abstract

Influenza virus infection is an ongoing health and economic burden causing epidemics with pandemic potential, affecting 5–30% of the global population annually, and is responsible for millions of hospitalizations and thousands of deaths each year. Annual influenza vaccination is the primary prophylactic countermeasure aimed at limiting influenza burden. However, the effectiveness of current influenza vaccines are limited because they only confer protective immunity when there is antigenic similarity between the selected vaccine strains and circulating influenza isolates. The major targets of the antibody response against influenza virus are the surface glycoprotein antigens hemagglutinin (HA) and neuraminidase (NA). Hypervariability of the amino acid sequences encoding HA and NA is largely responsible for epidemic and pandemic influenza outbreaks, and are the consequence of antigenic drift or shift, respectively. For this reason, if an antigenic mismatch exists between the current vaccine and circulating influenza isolates, vaccinated people may not be afforded complete protection. There is currently an unmet need to develop an effective “broadly-reactive” or “universal” influenza vaccine capable of conferring protection against both seasonal and newly emerging pre-pandemic strains. A number of novel influenza vaccine approaches are currently under evaluation. One approach is the elicitation of an immune response against the “Achille’s heel” of the virus, i.e. conserved viral proteins or protein regions shared amongst seasonal and pre-pandemic strains. Alternatively, other approaches aim toward eliciting a broader immune response capable of conferring protection against the diversity of currently circulating seasonal influenza strains.In this review, the most promising under-development universal vaccine approaches are discussed with an emphasis on those targeting the HA glycoprotein. In particular, their strengths and potential short-comings are discussed. Ultimately, the upcoming clinical evaluation of these universal vaccine approaches will be fundamental to determine their effectiveness against preventing influenza virus infection and/or reducing transmission and disease severity.

From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach

“…Despite recent efforts in basic and translational influenza and coronavirus research, there is still no vaccine against coronaviruses for use in humans (this includes SARS and MERS) [16][17][18][19]. In addition, there is yet no universal influenza vaccine available against all influenza virus subtypes and hence seasonal influenza vaccines have to be updated annually and that vaccines for pandemic preparedness are a challenge [20][21][22][23][24][25]. The lack of preventive vaccines for clinical use in humans against such viruses makes emerging influenza and coronaviruses a serious global threat.…”

Passive immunization with influenza haemagglutinin specific monoclonal antibodies

“…A number of strategies to develop a universal influenza vaccine are being pursued including targeting cellular immune responses to conserved epitopes, sequential immunisation with antigens expressing distinct head and conserved stem domains and computationally designed HAs to protect against past, present and potentially future influenza virus strains. 77 There is limited use of passively administered influenza virus-specific antibodies for prophylaxis or therapy. Concerns about the use of antibodies include cost, storage, shelf-life and the development of anti-drug antibodies.…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…These vaccines, however, cannot effectively protect against newly emerging viruses with antigenic shift and drift. 108,109 Antigenic drift results in changes in the antigenic site (a minor change) while antigenic shift results in a new virus subtype. Hemagglutinin and neuraminidase are the two enzymes dictating the antigenic properties of the viruses.…”