Currently available influenza vaccines may be trivalent or quadrivalent. Trivalent vaccines contain 2 influenza A strains and 1 influenza B strain, while quadrivalent vaccines contain the same 3 strains plus an extra B strain. There is no cross-protection from the B strain in the trivalent vaccine to the different B lineage represented in the quadrivalent vaccine. Eventually, all influenza vaccines will likely be quadrivalent, but, until then, the priority is to have enough vaccines for everyone in a given year. 

The composition of influenza vaccines is selected based on year-round surveillance data from more than 100 influenza centers in more than 100 countries. These data help to predict which strains are the most likely to circulate during the coming season. The World Health Organization recommends the strains that should be used to manufacture each season’s vaccines, but the US Food and Drug Administration (FDA) ultimately decides the vaccine constituents for the United States. Indeed, formulating the annual influenza vaccines is a complex and somewhat speculative endeavor that must start well ahead of each season; in the United States, the process begins in February. Not only must the strains chosen for the vaccines match the viruses expected to circulate in the subsequent season but they must also generally replicate well in eggs (and the nasopharynx, as in the case of the live attenuated influenza vaccine). Not all strains do, however. The influenza A virus H3N2, for example, is difficult—but not impossible—to grow in eggs. Two different vaccines must also be developed for the northern and southern hemispheres because the seasonality differs between the two. The FDA Center for Biologics Evaluation and Research’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) met on March 4, 2020, and the VRBPAC recommended that 2020-2021 northern hemisphere influenza vaccines contain components as described in the Centers for Disease Control and Prevention’s Immunization Works  March 2020 newsletter. Several vaccine components were updated. The recommended influenza vaccine composition is announced months in advance of each season to allow adequate time for manufacturing. As with the 2019-2020 season, options for the 2020-2021 flu season again include the live attenuated nasal spray in addition to injected forms of the vaccine.

Investigators have been working to develop a universal influenza vaccine that would mitigate many of the challenges associated with vaccine development. Specifically, attempts have been made at developing a universal influenza vaccine that would use conserved epitopes across all influenza viruses, but none of these attempts are sufficiently advanced yet to discuss licensure. Nevertheless, some of the knowledge gained from the research may lead to improvements in our established influenza vaccines.