virology blog

Influenza is an acute respiratory disease that occurs both in yearly outbreaks, or epidemics, and in much larger, global outbreaks called pandemics. Predicting the next pandemic strain is an important goal because advance preparation of a vaccine could save many lives.

The outbreaks of avian influenza in east and southeast Asia in 2003-2004 has lead to speculation that the next influenza pandemic is at hand. These H5N1 viruses cause disease in millions of domestic birds such as chickens, and furthermore have been shown to infect humans. Time magazine recently ran a cover story on this issue, entitled “Bird Flu Is Asia hatching the next human pandemic?”.

Do the avian H5N1 strains pose a threat to humans? There is no doubt that these viruses can infect and cause disease in humans. The real question is can they be efficiently transmitted from humans to humans, a requirement for a pandemic strain. Some scientists feel that it is only a matter of time before the viruses acquire this property. Or is it?

Avian H5 influenza viruses have apparently been infecting humans for years. In a 1992 study published in Seminars in Respiratory Infections, KF Shortridge and colleagues report significant levels of antibodies against the H5 virus in Asian populations. For example, 7% of sera sampled in Jiangsu Province of China were positive for antibodies against H5 virus. In a region with millions of inhabitants, this number represents a high level of infection. The conclusion is that H5N1 viruses have been infecting humans for years with little consequence. It therefore seems unlikely that these viruses pose any significant threat to humans.

There have been some reports that H5N1 viruses can be transmitted from human to human. All of these reports originate in Asia where it is difficult to determine if the virus that infected multiple household members came from a human, or a bird living in close proximity. To date there are no reliable data which suggest human to human transmission of H5N1 viruses.

The cycling of influenza virus strains in the recent past suggests a different candidate for the next pandemic strain. The H1N1 strains circulated from 1918 until 1957. From that year until 1968, H2N2 strains were prevalent, followed by H3N2 strains. The H1N1 strains re-emerged in 1977. Today, both H3N2 and H1N1 strains cause yearly epidemics of influenza. If influenza strains re-emerge when existing immunity wanes, then it would seem that the next pandemic strain would be an H2N2 strain. Since these strains stopped circulating in humans in 1968, anyone born after that year would be susceptible to infection with an H2N2 virus, because they would have no previous immunity.

In my opinion, we should stop worrying about avian influenza and concentrate on H2N2 strains as the next pandemic influenza virus.

This past week the vaccine against influenza made world news when the British government suspendend the manufacturing license of a Liverpool factory that produces the vaccine. The factory is owned by Chiron, which had hoped to sell influenza vaccine produced there in the U.S. As a consequence, the U.S. will fall about 48 million doses short of the 100 million doses of vaccine that should have been available this winter. Another producer of influenza vaccine, Aventis, will supply 54 million doses to the U.S. A very different influenza vaccine is produced by MedImmune – a live virus preparation sprayed into the nose – but only 1-2 million doses of that vaccine will be available.

As Dr. Robert Webster of St. Jude’s has said, “This is unacceptable in the United States. It is a bloody scandal”. Why is the U.S. caught in this position? Because vaccine manufacturing is a for-profit industry. Although this approach has been successful in the past, it is no longer viable.

Thirty years ago, there were numerous manufacturers of influenza vaccine – as many as 25. Today there are just three. There are no manufacturers of the poliovaccine in the U.S. – our supply of inactivated poliovirus vaccine is provided by Aventis. The lack of plentiful virus vaccine manufacturers can be readily explained: vaccine manufacturing is a risky business with low profit margins. Vaccines are expensive to develop and produce, and litigation over side effects further increases the cost.

The solution to this problem, to which I have subscribed for many years, is to transfer viral vaccine development and manufacturing from the private sector to the U.S. government. Vaccine institutes could be established throughout the U.S. where the manufacture of influenza, poliovirus, and other vaccines could be carried out. These vaccines would be sold by the government at low cost, not only to the U.S. but to other countries who require them. What better way to propagate global goodwill than to sustain life, rather than terminating it?

The U.S. has already taken a small step towards this plan by establishing the Vaccine Research Center. However, I envision a much broader initiative where such centers not only develop new vaccines, but manufacture and distribute existing products such as the influenza virus vaccine.

My colleagues have criticized this plan because it prevents scientific innovation. I do not believe a government run vaccine facility need be devoid of scientific creativity. The National Institutes of Health is an example of a government research facility that conducts outstanding scientific research. The key is to attract the best scientists, and provide them with a flexible, stimulating, and scholarly atmosphere in which to exercise their talents.

In “The River: A Journey to the Source of HIV and AIDS”, Edward Hooper claims that HIV-1 was introduced into humans in Kisangani, Democratic Republic of the Congo in the 1950s. He suggests that the stocks of oral poliovirus vaccine (OPV) that were being used in clinical trials were produced in cultures of kidney cells from chimpanzees that were infected with simian immunodeficiency virus, SIV, the predecessor of HIV.

Hooper’s hypothesis has been convincingly shown to be incorrect by a number of independent investigations. For example, analysis of the OPV used for the Congo trials revealed that it was not produced in chimpanzee cell culture (Nature. 2001 Apr 26;410(6832):1035-6). In addition, the strains of SIV that circulate in chimpanzees in the Congo are distinct from all strains of HIV-1 (Nature. 2004 Apr 22;428(6985):820).

A recent article by Paul Osterrieth (Oral polio vaccine: Fact versus fiction) provides the final death knell for Hooper’s hypothesis. According to Hooper, Dr. Osterrieth was responsible for preparing kidney cell culture from chimpanzees and using these cultures to prepare the stocks of OPV used in the Congo trials.

Osterrieth categorically denies that he ever sacrificed chimpanzees to produce kidney cell cultures, and states that he never prepared any poliovirus in cell culture. The article is well worth reading because it highlights the non-scientific means used by Hooper to support his now defunct hypothesis. As Osterrieth writes, “Mr. Hooper’s method is to take any word slip or hesitation and to convert it into a mysterious allusion to hidden crimes. This is the way of a prosecutor, not an investigator, and it has more to do with science fiction than fact.”