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Analysis

Do we need a new approach to making vaccine recommendations?

BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h308 (Published 30 January 2015) Cite this as: BMJ 2015;350:h308

Rapid Response:

Re: Do we need a new approach to making vaccine recommendations?

I appreciate the light shed by Natasha Crowcroft and colleagues about Bexsero and recommendations for vaccines in general. I particularly agree with the statement that “options need to be placed in the context of all healthcare, not just compared with other vaccines”.

In fact, new vaccines are preventive tools for diseases that are more and more rare, so that no benefit can be identified at a public health and statistical level, although they are more frequently recommended for mass vaccination. Which in turn, automatically and mathematically, increases the probability that the risks overweigh the benefits of a vaccine at a public health level.

So, the main ethical issue in this debate is to have irrefutable and methodologically rigorous clinical trials interpreted by scientists and agency officers that have no competing interests, which is not actually the case.

Since a vaccine is designed for mass vaccination this means a long term and a public health perspective that seems rather inconsistent with the limited vision of a charity centered on a particular disease and with the short term profit outlook of pharmaceutical companies.

Also, with the Vioxx scandal, the passive surveillance of vaccines and drugs has proved ineffective to detect much more frequent adverse effects that those that would reverse the benefit risk balance for a vaccine designed for such a rare condition, there other realistic concerns that have to be taken into account.

These concerns are about fundamental science and virology and are disregarded when assessing a vaccine. In fact I’ve noticed we don’t talk anymore about science when we talk about vaccines. We talk about money, emotion, belief and technology. Nevertheless the scientific point of view is most relevant for this topic.

Jean-Louis Velizier, a now retired virologist, had anticipated, in the early nineties that, as technology allows that, pharmaceutical industry could be tempted to use little proteins or even peptides to make up vaccines instead of whole bacteria or virus. And he warned that this strategy wouldn’t be correct, because, first, little proteins and peptides immunogenicity is very poor and this would bring to use more and more adjuvant in vaccine. This was true and squalene adjuvant of Pandemrix, the influenza vaccine used in most European countries during the pandemic episode, is thought to have caused narcolepsy. And second, the adjuvant only enhances quantitatively the immunogenic response, but an adjuvant can’t replace the dissection of a virus by T lymphocytes, or the intrastructural and tridimensional recognition of molecules by B and T lymphocytes.

Some will say that is only theory and that has nothing to do with empiric science, which is the only one that matters.
But sometimes is useful to have some knowledge about fundamental science to understand rather strange phenomenon.

I would give just a few examples.

First, acellular pertussis vaccine, for whooping cough, which immunogenicity has been shown to be waning with boosters and in the general population [1]. This is probably related to the capacity of B pertussis to evolve and to adapt to the vaccine that is a chimera created by technology and doesn’t exist in the world. New emergent strains of B Pertussis don’t bear anymore pertactin which is a main component of the vaccine, and then make the vaccine ineffective [2].

A second example, is the Sanofi blockbuster, Menactra, which is a quadrivalent meningococal vaccine designed for serotypes A, C, Y and W 135 combined with a diphtheria toxoid conjugate vaccine. After introducing the vaccine in 2007 in the United States the Advisory committee for immunization practices (ACIP) recommended the vaccine for adolescents from 11 to 18 years. In 2011 a number of cases of meningitis in vaccinated adolescents (mean time 3,25 years after vaccination) lead to new recommendations adding a booster at the age of 16 [3].

In my opinion, this shows that a long term vision in needed, ant this kind of vision is rather inconsistent with the way the decisions are taken in this field.

[1] Nicolas P Klein and coll, Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in Children. N Engl J Med 2012; 367:1012-1019
http://www.nejm.org/doi/full/10.1056/NEJMoa1200850
[2] Seppa N. Whooping cough bounces back. Science News, april 2014. https://www.sciencenews.org/article/whooping-cough-bounces-back

[3] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6003a3.htm

Competing interests: No competing interests

13 February 2015
Claudina MICHAL-TEITELBAUM
Preventive care for children, MD
Lyon, France
personal 169 chemin de la rivière 01480 MESSIMY SUR SAONE