Current and future influenza vaccines

Abstract

Although antiviral drugs and vaccines have reduced the economic and healthcare burdens of influenza, influenza epidemics continue to take a toll. Over the past decade, research on influenza viruses has revealed a potential path to improvement. The clues have come from accumulated discoveries from basic and clinical studies. Now, virus surveillance allows researchers to monitor influenza virus epidemic trends and to accumulate virus sequences in public databases, which leads to better selection of candidate viruses for vaccines and early detection of drug-resistant viruses. Here we provide an overview of current vaccine options and describe efforts directed toward the development of next-generation vaccines. Finally, we propose a plan for the development of an optimal influenza vaccine.

Figure 1.. Real-time tracking of influenza virus epidemics.

This is a screen shot of a phylogenic tree based on the HA sequences of human A(H3N2) viruses isolated between 2016 and 2018 generated by the website ‘next strain’ (https://nextstrain.org/). Subclades (3c2, A1, A1b, and A1a, etc.) are indicated by grey letters and regions where the isolate was isolated are indicated by each color (listed at the upper left).

Figure 2.. Antigenic drift.

(1) Immunologically naïve human populations are attacked by an influenza virus. (2) Infected individuals acquire immunity against influenza virus. (3) Viruses accumulate amino acid mutations in their HA during replication. (4) Some individuals who do not possess immunity against the initial virus are attacked by the mutated virus. (5) Infected individuals acquire immunity against this virus. (6) The virus further accumulates amino acid mutations in its HA. (7) The remaining naïve individuals are attacked by this further mutated virus. (8) The majority of the individuals in human populations eventually acquire immunity against these viruses. They are then protected from influenza viruses with similar antigenicity. (9) The virus obtains one or two mutations in its HA that substantially alter antigenicity (i.e., antigenic drift). (10) The antigenically drifted virus can infect individuals who possessed immunity against the previously circulating viruses. (11) The individuals infected with the antigenically drifted virus mount immunity to this virus. The cycle continues.

Figure 3.. Immunologic imprinting by influenza A viruses during childhood.

Immunologic imprinting varies from generation to generation because the circulating influenza A viruses in childhood differ. For individuals born between 1918 and 1957, between 1957 and 1968, between 1968 and 1977, between 1977 and 2009, or after 2009, their first encounter with an influenza virus would have been with H1N1, H2N2, H3N2, H1N1 or H3N2, or H1N1pdm09 or H3N2 virus, respectively. Even though the virus subtypes were identical between these periods, the antigenicity of the viruses changed over time. Therefore, infections during childhood immunologically imprinted the infected individuals in a variety of ways. This imprinting affects immune responses to subsequent virus infection and vaccination.