A potential mismatch between the current flu vaccine and a strain of H3N2 influenza that has caused severe infections in the Southern Hemisphere suggests this may be a harsh season in the United States and underscores the need for new vaccine production methods, public health officials emphasized in a recently published commentary.1

More specifically, flaws in the use of chicken eggs as the primary vaccine production platform likely resulted in the problem, which led to a higher number of severe infections and deaths during the flu season in Australia.

“Given that most of the U.S. influenza vaccine supply is currently produced in eggs and the composition of the 2017-2018 Northern Hemisphere vaccine is identical to that used in Australia, it is possible that we will experience low vaccine effectiveness against influenza A (H3N2) viruses and a relatively severe influenza season if they predominate,” the authors noted. “This possibility underscores the need to strive toward a ‘universal’ influenza vaccine that will protect against seasonal influenza drift variants as well as potential pandemic strains, with better durability than current annual vaccines. Among other advantages, in all likelihood, such a vaccine would not be subject to the limitations of egg-based vaccine technology.”

The Holy Grail of flu prevention, a universal vaccine, would likely be created in cell culture and wouldn’t be vulnerable to the limitations of egg-based production.

One of the co-authors of the paper, Anthony Fauci, MD, director of the NIH National Institute of Allergy and Infectious Diseases, emphasizes that a new universal flu vaccine that would be effective against multiple strains of virus is particularly needed before the next flu pandemic hits. The emergence of pandemic flu virus H1NI in 2009 and the subsequent rush to create a vaccine revealed a vulnerability in the current approach. The antigenic “shift” of flu virus into a pandemic strain — as opposed to the milder antigenic “drift” that occurs seasonally — could result in a virus much more virulent than the 2009 strain.

“We were really fooled,” Fauci said recently in San Diego at the IDWeek 2017 conference. “While everybody was looking to the Far East, this [pandemic strain] broke out in California and Mexico.”

The first cases appeared in March 2009, and Fauci and other public health experts said a vaccine would be needed by the following winter for the flu season. However, the virus struck in greater numbers much earlier than projected — before the vaccine was available — as children returned to school in the fall of that year.

“The lesson here is the inadequacy in how we respond from a vaccine standpoint to outbreaks. [We told Congress] it’s April, we know what it is, and we are almost certain that we will see this in the following season in the winter of 2009-2010.”

Citing the typical six-month estimate to create a new flu vaccine, public health officials projected that immunization with an H1N1 pandemic vaccine should be possible in October 2009. By then, the virus was widely circulating.

“The outbreak occurred before the vaccine became available,” Fauci said. “What this lesson told us is that we certainly need a universal influenza vaccine, without a doubt, to take off the table the drifts and the shifts, and the lack of preparedness.”

10% Efficacy?

In the commentary, Fauci and co-authors said the immediate concern is the H3N2 virus that hit Australia and may now strike the U.S. in the 2017-2018 flu season.

“Reports from Australia have caused mounting concern, with record-high numbers of laboratory-confirmed influenza notifications and outbreaks and higher-than-average numbers of hospitalizations and deaths,” they noted. “The number of notifications reached 215,280 by mid-October, far exceeding the 59,022 cases reported during the 2009 H1N1 influenza pandemic, according to the Australian Government Department of Health. H3N2 viruses predominated, and the preliminary estimate of vaccine effectiveness against influenza A (H3N2) was only 10%. The implications for the Northern Hemisphere are not clear, but it is of note that the vaccine for this upcoming season has the same composition as that used in the Southern Hemisphere.”

It appears this paltry 10% efficacy against H3N2 in the current vaccine was caused less by viral mutation in nature than by changes that occurred during egg-based vaccine production.

“[The] egg-propagated vaccine viruses acquired changes in the HA [hemagglutinin] that subsequently altered antigenicity against circulating strains,” they concluded. “This observation lends credibility to the hypothesis that egg-adapted changes contribute to poor influenza vaccine effectiveness.”

Vaccination still is highly recommended, and the level at which H3N2 will ultimately circulate in the U.S. was unknown as the current flu season began.

“However imperfect, though, current influenza vaccines remain a valuable public health tool, and it is always better to get vaccinated than not to get vaccinated,” the authors concluded. “Although targeted research to improve current vaccine antigens, platforms, and manufacturing strategies may in the short-term lead to enhanced effectiveness of seasonal influenza vaccines, to achieve the ultimate objective of a universal influenza vaccine, a broad range of expertise and substantial resources will be required to fill gaps in our knowledge and develop a transformative approach to influenza-vaccine design.”

Airborne Spread?

Typically, when a novel virus or pandemic flu strain emerges, the CDC recommends more stringent PPE than normally used by healthcare workers. There has been ongoing debate, and sometimes controversy, about whether influenza virus is spread almost exclusively by droplets and source contact, or whether it can spread beyond an index case in the manner of a true airborne virus like measles.

Recent research supports “the idea that airborne infectious particles could play an important role in the spread of influenza,” the National Institute for Occupational Safety and Health (NIOSH) reports.

“Influenza is known to be transmitted through respiratory secretions containing the virus,” notes William G. Lindsley, PhD, a research biomedical engineer in the NIOSH Health Effects Laboratory Division. “Airborne transmission of influenza by small aerosol droplets over longer distances is debated in the literature.”

In a blog post2 citing NIOSH research, Lindsley argued that healthcare workers and other patients may need to be better protected from those with influenza if airborne transmission is verified.

NIOSH researchers studied 53 volunteers positive for influenza A.3 They found that 28 (53%) produced aerosol particles containing viable virus during coughing. In addition, 22 (42%) produced aerosols with viable virus during exhalation. Thirteen subjects had both cough aerosol and exhalation aerosol samples that contained the flu virus, Lindsley reported.

“Because individuals breathe much more often than they cough, these results suggest that breathing may generate more airborne infectious material than coughing over time,” he noted. “On the other hand, as coughing involves much higher air velocities than breathing, coughing may spread the virus further in a given location. Thus, both mechanisms for producing infectious aerosols may be important depending upon such factors as the distance from a patient, the timescale, the infectious dose, and the air flow within a room.”

REFERENCES

1. Paules CI, Sullivan SG, Subbarao K, et al. Chasing Seasonal Influenza — The Need for a Universal Influenza Vaccine. New Engl J Med Nov.29, 2017. DOI: 10.1056/NEJMp1714916

2. Lindsley WG. Flu Virus Generated in Coughs and Exhalations. NIOSH Science Blog, Nov. 9, 2017. Available at: http://bit.ly/2zS91WQ. Accessed Nov. 30, 2017.

3. Lindsley WG, Blachere FM, Beezhold DH, et al. Viable influenza A virus in airborne particles expelled during coughs versus exhalations. Influenza Other Respir Viruses 2016;10(5):404-413.