Sensationalist Hyperbole from the NY Times, Re vaccine adjuvants

Andrew Pollack is an MIT-trained engineer, who has covered the business and science of biotechnology for the New York Times since 2000. I don't know how qualified he is to comment on aspects of biology and medicine, or indeed how far he understands the topics that he speaks about. But it irritates me greatly when I see sensationalist tripe, such as, "Are Americans obligated to use an unproven vaccine to help protect people in other countries from the flu pandemic?" with which Pollack opens his commentary in yesterday's NY Times - curiously titled, 'Benefit and Doubt in Vaccine Additive' - on the use of adjuvants in vaccines in the United States.

The question is, or rather is meant to be, a loaded one; note the use of the key terms - 'obligated', 'unproven vaccine', and 'protect people in other countries' - that are guaranteed to rouse the rabbles and sit well with the proponents of anti-vaccination lunacy in the US. Let me first take the words that were surely utilized to engender a sense of outrage, and tickle the xenophobia inherent in many of that lunatic fringe: 'obligated', and 'protect people in other countries'.

As far as vaccines are concerned, there is no 'obligation' for the people of this country - but it does make eminently good sense. Consider the case of the influenza virus, which has been has been one of the major causes of morbidity and mortality, especially among young children, since 1918. The commonly circulating strain of the virus (the seasonal 'flu') is not virulent enough to cause mortality, but the virus is able to mutate at a very high rate leading to the emergence of highly virulent strains, which have a range of hosts, including humans, horses, pigs, sea mammals and birds, and more importantly, some of which are able to cross the species barrier (for example, bird to human, avian influenza A H5N1). When a new (mutated) influenza virus appears against which the human population has no immunity, it has the potential of causing a pandemic. Pandemics caused by influenza A viruses in the past have been associated with high morbidity and mortality, as well as loss of livelihood.

It does not take great intelligence to understand that geographical barriers are largely meaningless nowadays, what with the tremendous increase in global travel, urbanization, as well as overpopulation; any epidemic, particularly the ones due to the hypervirulent new influenza strains (including those crossing over from animals) is likely to disseminate globally rather quickly, leading to disease and deaths in large numbers, as we have seen several times in the past few years, making the occurrence of the next pandemic just a matter of time. Therefore, the 'protect people of other countries' argument does not wash at all.

Let's consider next the question of 'unproven vaccine'. There is no doubt that vaccines are the most powerful prophylactic (sometimes, also therapeutic) tool for control of many infectious diseases of public health significance, including influenza. Let's see how it applies to the novel influenza A (H1N1), for which the World Health Organization raised the worldwide pandemic alert level to Phase 6, on June 11, 2009. The CDC reports that this "action was a reflection of the spread of the new H1N1 virus, not the severity of illness caused by the virus. At the time, more than 70 countries had reported cases of novel influenza A (H1N1) infection and there were ongoing community level outbreaks of novel H1N1 in multiple parts of the world... Since the WHO declaration of a pandemic, the new H1N1 virus has continued to spread, with the number of countries reporting cases of novel H1N1 nearly doubling."

A valuable commentary in the Virology journal by William Gallaher, a Professor Emeritus of the Louisiana State University Health Sciences Center, uttered the necessary words of caution and prudence:

Actions concerning Flu H1N1 2009 need to be based on fact and science, following recommendations of public health officials, and not fueled by political, legal or media interests and hysteria. This is time for calm, thoughtful action, and not the panic we have seen spread around the globe inspired by media reports.

And most importanly,

Every influenza outbreak or pandemic is unique, so the facts of each one must be studied before an appropriate response can be developed... The only really accurate assessments have been retrospective, after years or decades of further analysis, so it is important for both the scientific and general public to understand that decisions will need to be made using the best information available at the time and will be fallible. There can be no standard playbook. However, fallible does not mean irrational.

He cautions:

Even though elected and corporate officials are charged with the responsibility to make such decisions, and no one wishes to be found negligent in retrospect, the best course is to closely follow the recommendations of recognized experts in the field of influenza virology and public health who have made the study and understanding of this viral disease their life's work. The WHO, CDC, academic virologists and physicians, and state epidemiologists know their business and should be trusted to guide public policy. An elected official cannot and should not try to reproduce and override, with an hour's briefing, their cumulative decades of experience. This is no time to haul out tired agendas concerning immunization or immigration or cultural and ethnic biases, using influenza for cover.

This needs to be emphasized and re-emphasized. The media should not, and certainly not for an esteemed newspaper such as the New York Times, knowingly or unknowingly collude with the anti-vaccination crowd in spreading misinformation at this crucial juncture.

Influenza H1N1 2009 virus is in the family of H1N1 viruses; however, changes in its genome sequence indicate a significant antigenic shift in both surface antigens, hemagglutinin (H) and neuraminidase (N). And it is possible that the virus may mutate further, become better adapted to human replication and spread in the coming months. Therefore, it is important to plan ahead considering a continued circulation of an enhanced H1N1 2009 virus, and keep vaccine development studies going based on the novel H and N antigens. As Professor Gallaher concludes:

The future course of the outbreak cannot be predicted, but prudence dictates that a new influenza vaccine, targeted to the novel influenza H1N1 2009 sequence be quickly developed and prepared for worldwide administration. In the absence of existing human "herd" immunity to this virus, only immunization provides a significant hope of suppressing the long-term impact of this newly emergent virus.

The H1N1 vaccine, therefore, builds on previous experience, and uses rationally sound scientific principles, using epidemiological and molecular biological tools. Therefore, the question of 'unproven vaccine' is disingenuous at best. What is Pollack's beef with the vaccine, then?

Ah, it turns out that he focuses the rest of his article to bash on adjuvants. In the context of vaccines, adjuvants are substances, either chemical (such as aluminium hydroxide, or lipid based carrier systems) or biological (such as CpG oligonucleotides or an emulsified mixture of antigens), often included with the vaccine formulations, in order to enhance the immunological effects of the vaccine. Adjuvants have few direct effect when given by themselves. In conjunction with the vaccine, adjuvants activate and direct the innate and adaptive immune responses to the vaccine antigens, which may often be rather poorly immunogenic by themselves. An extensive review of adjuvant action is here and here.

Even while Pollack acknowledges the fact that "one reason to use adjuvants is that they can increase a vaccine’s potency against a virus to which it is poorly matched", and also that Canada and European nations (not to mention Asian nations) routinely use vaccines with adjuvants, he continues to fan the irrational fear of the adjuvants by projecting it as the great unknown, and using pointed language, such as:

American officials have decided against it for now. They say that... the safety of the additives has not been proved.

and quote-mining public health officials out of context,

"There’s just more uncertainty" (Jesse Goodman, chief scientist at the FDA); "If you add what the public would perceive as another unknown there, there’s a concern that people would be reluctant to get vaccinated" (Tony Fauci, Director of the NIAID).

Current trial vaccines active against the H1N1 2009 virus have been known to engender a strong immune response on their own. But as Professor Gallaher had cautioned, this virus in the population may mutate quickly requiring additional help in form of adjuvants. Besides using adjuvants may be necessary to generate adequate immunse response in people with weak or weakened immune system, such as children or the elderly.

Overall, Pollack's write-up is a weird mishmash of information that hardly offers any positive outlook towards adjuvants and vaccination in general, and its negative connotations can only serve to confirm the irrational fears and biases, further confuse the already-confused vaccine-hesitant sub-population, and cheerlead the anti-vaccination loons. Thoughout, he keeps strangely projecting the adjuvants as an issue of increasing the existing stock of vaccines, and not of its immunological efficacy. Is this the standard of science reporting one expects from the New York Times?

Further reading:

• Palese P (2004) Influenza: Old and new threats. Nature Medicine, 10: S82
• Webby RJ and Webster RG (2003) Are we ready for pandemic influenza? Science, 302: 1519
• Stephenson I, et al. (2004) Confronting the avian infl uenza threat; vaccine development for a potential pandemic. Lancet, 4: 499
• Writing committee of the second World Health Organization (2008) Consultation on clinical aspects of human infection with avian infl uenza A (H5N1) virus. Update on avian influenza A (H5N1) virus infection in humans. New England Journal of Medicine, 358: 261–73
• Gallaher WR (2009) Towards a sane and rational approach to management of Influenza H1N1. Virology Journal, 6:51
• Schijns VEJC (2003) Mechanisms of vaccine adjuvant activity: initiation and regulation of immune responses by vaccine adjuvants. Vaccine, 21: 829

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UPDATE: revere of the Scienceblogs, a senior epidemiologist and public health scientist, had already weighed in on the topic of flu virus, vaccines and adjuvants. It is an enjoyable and informative read. Methinks Pollack would have done well to read this post before writing his stuff!