TWiV 396: Influenza viruses with Peter Palese

TWiVVincent speaks with Peter Palese about his illustrious career in virology, from early work on neuraminidases to universal influenza virus vaccines, on episode #396 of the science show This Week in Virology.

You can find TWiV #396 at microbe.tv/twiv, or listen below.

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Edwin D. Kilbourne, MD, 1920-2011

Edwin Kilbourne MDFrom the New York Times:

Dr. Edwin D. Kilbourne, a medical researcher who figured out how to outwit fast-evolving flu germs, developing a new vaccine each year by intermingling genes of different disease strains, died Monday in Branford, Conn. He was 90.

I’m saddened by Dr. Kilbourne’s passing – he was the Chairman of the Department of Microbiology at Mt. Sinai School of Medicine, New York, during the years when I did my Ph.D. research. Dr. Kilbourne had many accomplishments during his research career, but three stand out in my mind. First, he devised a method for producing high-yielding recombinant vaccine strains. The seasonal influenza virus strains often do not multiply well in embryonated eggs; he solved this problem by crossing them with a virus strain, called PR8, known to propagate well in that host. Such strains were produced by co-infecting cells with the seasonal strain selected as a vaccine candidate, and the PR8 strain. Viruses selected for vaccine production inherited two RNA segments from the seasonal strain – encoding the HA and NA glycoproteins – and the remainder from PR8. This method is still used today in influenza vaccine production.

I also recall Dr. Kilbourne’s role in the swine influenza immunization of 1976. Two years after I joined the Department of Microbiology, an outbreak of swine influenza was identified in Fort Dix, N.J. At the time it was believed that a swine virus had caused the 1918-19 influenza pandemic. Therefore scientists were concerned that the virus had returned to Fort Dix and would soon cause another catastrophic outbreak. Dr. Edwin Kilbourne and others convinced the US Public Health Service to conduct an mass immunization campaign against the virus.

The third event that stands out in my mind is more personal. I had befriended Dr. Kilbourne’s son, Ed, while attending Cornell University from 1970-74. In the summer of 1975 I visited Ed at his parents’ home in northern NJ, and after dinner Dr. Kilbourne joined the conversation. He asked me what I planned to do with my life, and I told him that I wanted to study microbiology, but I was not sure where I should do that. In fact I had applied, with little direction, to a few local colleges to earn a masters degree. Dr. Kilbourne said, without hesitation, ‘You should get your Ph.D. at Mt. Sinai’. The next day I applied to the program, was accepted, and began my Ph.D. studies in the fall. The next year I joined Dr. Peter Palese’s lab and began my career in virology.

I remember that Dr. Kilbourne always wore a tie and laboratory coat, and that he brought his lunch on a cafeteria tray to department seminars. I’ll always remember and appreciate the excellent career advice that he provided to me.

Update: I remembered today that I once had the occasion to sit next to Dr. Kilbourne on an airplane, returning home after a scientific meeting. When he ordered a martini he seemed slightly embarrassed. He looked at me with a mischievous twinkle in his eye and said ‘You’ll find as you get older you will need one of these at the end of the day”.

Pandemic influenza vaccine was too late in 2009

Influenza researcher Peter Palese visited yesterday and spoke about “Pandemic influenza: Past and Future”. A key part of his talk was a review of his efforts to produce a universal influenza vaccine which protects against all strains. He used the following graph to make the point that when influenza pandemic strains emerge, there is insufficient time to deliver a vaccine using current technology.

influenza like illness and vaccine distributionImage source: CIDRAP

The graph depicts the percentage of visits for influenza-like illness (ILI – the red line) and distribution of the swine-origin influenza vaccine (blue line) from September 2009 to May 2010 in the US. At the peak of ILI at the end of October 2009, fewer than 20 million doses of vaccine had been shipped. By the time 120 million doses had been distributed, infections with the new H1N1 strain had subsided. Dr. Palese believes that immunization was too late to have a substantial impact on this second wave of influenza. The inability to immunize the population in time to prevent influenza was conceded by the Centers for Disease Control and Prevention in October 2009.

Dr. Palese’s solution to this dilemma is to deploy universal vaccines which would protect against any influenza strain, including future pandemic viruses. He and others have already made impressive progress towards this goal.

The head of Columbia’s Environmental Health & Safety division pointed out to Dr. Palese that despite being delivered too late to prevent the second wave of influenza, the vaccine would be expected to reduce influenza during the 2010-2011 season in the US.

An interesting question is whether the additional cost of rushing production and development of the vaccine in 2009 was a worthwhile expenditure. In hindsight it would appear that the answer is no. But had the fall wave of influenza peaked later – December or January, for example – the vaccine might have been more effective in preventing infections. That’s why we’ll have to do the same when the next pandemic strain emerges – unless by then we have a universal influenza vaccine.

Thoughts on this season’s influenza vaccine

After my lecture on influenza pathogenesis and evolution at the Northeast Laboratory Conference 2010 in Portland, Maine, I was asked if it is necessary to receive the influenza vaccine every year. This question was precipitated by my statement that the 2010-11 trivalent influenza vaccine contains the same swine-origin H1N1 strain as last year’s monovalent vaccine. That virus has not undergone sufficient antigenic drift to necessitate the formulation of a new vaccine.

There are two main considerations* when deciding whether to be immunized yearly against influenza: the nature of the vaccine and age of the recipient. Last year’s seasonal influenza vaccine for the northern hemisphere contained the following strains:

  • A/Brisbane/59/2007 (H1N1)
  • A/Brisbane/10/2007 (H3N2)
  • B/Brisbane/60/2008

Also made available last year was a monovalent vaccine comprising the pandemic strain, A/California/7/2009.

Strains included in the 2010-11 vaccine are:

  • A/California/7/2009 (H1N1)
  • A/Perth/16/2009 (H3N2)
  • B/Brisbane/60/2008

The seasonal H1N1 strains of previous years are no longer circulating and have been eliminated from the vaccine. If you received last year’s seasonal vaccine and the monovalent vaccine, is it necessary to receive this year’s vaccine? The answer is yes, because the H3N2 strain is different – last year the vaccine contained a Brisbane strain while this year’s H3N2 isolate is from Perth. The full WHO report on strain selection is available as a pdf document.

What would be the answer if this year’s trivalent vaccine were identical to that used last year? The answer would still be to receive the vaccine, because the duration of immunity provided by the inactivated influenza vaccine has always been an issue. In elderly recipients (>65 years of age) immunity barely lasts for a single influenza season. Younger recipients will likely be protected from disease for one influenza season, and perhaps a second season as well, although in the latter case a milder respiratory disease may result. For these reasons the CDC recommends annual immunization against influenza virus for all individuals 6 months of age and older.

The current inactivated influenza vaccines were developed during World War II, and although they have since been refined and purified, there are still deficiencies, including brief duration of protective immunity. Development of new influenza vaccines that not only overcome this problem, but also provide broader protection, is clearly needed.

*This post, like everything else on virology blog, does not contain medical advice. It comprises scientific information about the vaccines which can be used, together with your health care provider, to reach a decision about immunization.

TWiV 99: ICAAC Boston 2010

Host: Vincent Racaniello

Vincent tours the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Boston, speaking with exhibitors and visitors, including Professors Derek Smith, Michael Schmidt, Frederick Hayden, and Myra McClure.

Many thanks to Chris Condayan and Ray Ortega of the American Society for Microbiology for recording and editing this episode.

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TWiV 95: Does a virus shift in the woods?

Hosts: Vincent Racaniello, Dickson DespommierAlan Dove, and Rich Condit

On episode #95 of the podcast This Week in Virology, Vincent, Dickson, Alan, and Rich consider the end of the influenza H1N1 pandemic, dengue in Florida, vaccinia virus infection in Brazilian monkeys, and viruses in the faecal microbiota.

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Alan – Families Fighting Flu
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Food, Inc.
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H1N1 pandemic is over

The World Health Organization has declared the end of the pandemic caused by H1N1 influenza virus. According to Director-General Margaret Chan,

The world is no longer in phase 6 of influenza pandemic alert. We are now moving into the post-pandemic period. The new H1N1 virus has largely run its course.

As we enter the post-pandemic period, this does not mean that the H1N1 virus has gone away. Based on experience with past pandemics, we expect the H1N1 virus to take on the behaviour of a seasonal influenza virus and continue to circulate for some years to come.

According to the Director-General, levels and patterns of H1N1 transmission are now different from those observed during the pandemic. Out-of-season outbreaks are no longer being reported, and their intensity is similar to that seen during seasonal epidemics. In addition, multiple influenza viruses are being isolated in many countries, a pattern typical of many recent seasonal epidemics.

I take particular interest in what the Director-General believes did not happen:

This time around, we have been aided by pure good luck. The virus did not mutate during the pandemic to a more lethal form. Widespread resistance to oseltamivir did not develop. The vaccine proved to be a good match with circulating viruses and showed an excellent safety profile.

I continue to wonder why the Director-General, and many others, feel that influenza virus must change to a more lethal form. Although the four previous influenza pandemics occurred in multiple waves of increasing lethality, there is no evidence that they are a consequence of viral mutation. For example, the only virus available from the 1918 pandemic was rescued from an Alaskan influenza victim who was buried in permafrost in November of that year, when higher mortality was already evident. This makes it impossible to correlate any genetic changes in the virus with increased virulence. Viruses are available from different stages of the pandemics of 1957 and 1968, which also occurred in waves of increasing lethality, but to my knowledge the virulence studies have not been done.

I believe that a major selective force for viral evolution is the need to maintain efficient transmission among hosts. This may be achieved by any number of phenotypic changes, such as increases in stability and virion production. Changes in lethality might also lead to more effective transmission – for example, by inducing more severe coughing, the virus could be better transmitted among humans. But there is no genetic evidence that such changes have occurred during influenza virus pandemics.

How has the idea that influenza virus mutates to greater lethality permeated our popular culture? I don’t know the answer, but John Barry’s The Great Influenza is a prime suspect.

TWiV 89: Where do viruses vacation?

Hosts: Vincent Racaniello and Alan Dove

On episode #89 of the podcast This Week in Virology, Vincent and Alan review recent findings on the association of the retrovirus XMRV with ME/CFS, reassortment of 2009 pandemic H1N1 influenza virus in swine, and where influenza viruses travel in the off-season.

Click the arrow above to play, or right-click to download TWiV #89 (56 MB .mp3, 78 minutes)

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AlanTree of Life graphic
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TWiV 77: Non-nuclear proliferation

Hosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich revisit circovirus contamination of Rotarix, then discuss poxvirus-like replication of mimivirus in the cell cytoplasm, and whether seasonal influenza immunization increases the risk of infection with the 2009 H1N1 pandemic virus.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $50 off a Drobo or $100 off a Drobo S.

Win a free Drobo S! Contest rules here.

Click the arrow above to play, or right-click to download TWiV #77 (60 MB .mp3, 83 minutes)

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TWiV 75: Rabies rampant

Hosts: Vincent Racaniello, Alan Dove, and Matthew Frieman

Vincent, Alan, and Matt review contamination of Rotarix with circovirus DNA, antigenic similarity between 1918 and 2009 H1N1 influenza, a collection of rabies reports, and chicken pox mistaken for smallpox in Uganda.

This episode is sponsored by Data Robotics Inc. Use the promotion code VINCENT to receive $50 off a Drobo or $100 off a Drobo S.

Win a free Drobo S! Contest rules here.

Click the arrow above to play, or right-click to download TWiV #75 (57 MB .mp3, 79 minutes)

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Matt Bitesize Bio
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