Have Researchers Finally Found the Key to a Universal Influenza Vaccine?

Investigators at the National Institute of Allergy and Infectious Diseases (NIAID) and the National Human Genome Research Institute (NHGRI) believe they have found the key to developing a universal vaccine for influenza.

In research published online on July 21 by the journal Cell, the scientists identified 3 distinct types of vaccine-induced antibodies that can neutralize diverse strains of group 1 and group 2 influenza A viruses. For this project, they examined blood samples from 6 people who had received a vaccine against H5N1 influenza and found B cells that reacted to various subtypes of influenza virus. The study subjects had been enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial.

According to the authors of the Cell paper, co-crystal structures with hemagglutinin revealed that each class of antibodies used characteristic “germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem.” They noted that all 6 study subjects had sequences from at least 1 multi-donor class. In half the subjects, multi-donor class sequences were recovered from >40% of cross-reactive B cells.

The researchers believe these findings demonstrate that vaccination with a divergent hemagglutinin can “increase the frequency of B cells encoding broad influenza A-neutralizing antibodies,” and they propose that the sequence signature-quantified prevalence of these B cells be used as a “metric to guide universal influenza A immunization strategies.”

At present, of course, the seasonal influenza vaccine must be updated each year to accommodate for influenza virus mutation. Although influenza virus mutates significantly from year to year, it is believed that the stem region of the virus typically remains unchanged. According to the authors of the Cell paper, this makes the stem “an ideal target for antibodies” for a universal flu vaccine. Previously, scientists had only been able to identify broadly neutralizing antibodies targeting the flu virus stem.

The hope is that a universal vaccine would be effective against multiple subtypes of influenza, eliminating the need to update the vaccine each year. This would result in huge cost savings and perhaps improve the efficacy of annual vaccination, reducing the healthcare burden associated with influenza. In the short term now, though, researchers can “use the B cell sequencing information… identified to quickly and accurately measure immune responses among participants in future influenza vaccine trials,” the authors noted in a NIAID statement released in conjunction with the publication of their findings.

In a review published in May in the journal Future Virology, South Korean researchers Yo Han Jang and Baik Lin Seong note that influenza A viruses are “broadly categorized into subtypes according to their surface glycoproteins hemagglutinin and neuraminidase.” The 18 hemagglutinin subtypes are further classified into 2 distinct phylogenetic groups. Although agencies such as the World Health Organization and the Centers for Disease Control and Prevention typically recommend the hemagglutinin and neuraminidase viral surface antigens for inclusion in the annual vaccine, the South Korean authors state that “the empirical nature of the recommendations, which basically amount to an educated guess [and] inevitably results in occasional vaccine mismatches.”

“The influenza virus, due to its segmented nature and intrinsically high mutation rate, is prone to frequent antigenic drifts and shifts, leading to annual episodes, as well as occasional pandemic outbreaks,” they write. “Vaccination has been considered the most effective way to control the influenza virus, but the seasonal influenza vaccines currently available only provide strain-specific protection. Developing a flu vaccine that offers universal protection against all influenza strains is thus tantamount to the quest for the Holy Grail.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.