Pertussis Vaccine Failure Should be a Wake-up Call

Whooping cough outbreaks have occurred with increasing frequency in the last year and are beginning to become major news items, as highlighted by major outbreaks on-going in California. In virtually every article, the disease is described as vaccine preventable and blame is often cast upon Jenny McCarthy and autism-crazed parents that frequently refuse vaccination. But the facts of the matter are not that simple.

Despite the recent press on the vaccine-autism debate, infant vaccination rates remain at or near all-time highs with 96.2% of infants getting at least three doses of DTaP in 2008 versus just 61% getting at least three doses of DTP in 1991 [1]. Furthermore, in recent outbreaks, a majority of affected have in fact been completely vaccinated (see NJ outbreak in which ALL affected children had been completely vaccinated). So given that the most at-risk population (children under 3 months) is not eligible for vaccination and their protection depends on the protection of older children, the real question to emerge from the recent pertussis outbreaks should be Why is the pertussis vaccine no longer as effective or as long lasting as it once was? People and public health agencies should be DEMANDING the answer to this question. They instead seem content with the possible addition of another booster of the DTaP to be given at seven years of age, thus increasing the number of doses of DTaP now given to American children to 6 and unnecessarily boosting tetanus and diphtheria in the bargain.

On a comical level, it is hard to imagine any other industry responding to the failure of their product by encouraging people to just buy more of the failing product. Do you want a second Toyota, just in case the first shoots off like a cannon? Yet this laughable marketing scheme seems to be just what Big Pharma has pulled off when it comes to DTaP. Their reward for a failing product is 20% higher sales of that very same product.

Historical Perspective

To fully understand the problems behind the failure of DTaP, we need a brief review of the history of pertussis vaccination. Use of the singular pertussis vaccine began in the US in the 1930s. By the 1940s, doctors and public health authorities switched to using DTP, a triple-vaccine designed to provide immunity against diphtheria, tetanus and pertussis. Overtime,

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however, a substantial number of adverse events resulting in permanent injury were found to be associated with the DTP vaccine (specifically the pertussis component), leading to the development of DTaP, which became available for use in 1991. The difference between the two vaccines is in the pertussis component. The previous (DTP) used whole-cell pertussis while the newer vaccine utilized acellular pertussis (hence the small a before the P in DTaP) which consists of selected purified pertussis antigens. Because of the lowered number of antigens presented, it is thought to have an increased safety profile and has demonstrated a substantial reduction in adverse events.

One could see why the whole-cell pertussis vaccine might be more effective in preventing pertussis disease than the acellular version. Quite simply, the whole-cell pertussis component more closely resembles actual infection with pertussis. Therefore, one could assume that the immune response generated by this challenge would be more effective in preventing natural infection. However, we need not rely on common sense alone, as the published scientific data confirms a key difference between the two vaccines.

Immunological Responses

The CDC reports that in the United States, cases of whooping cough have increased approximately 10-fold in the last twenty years [2], DESPITE AN INCREASE IN VACCINATION COVERAGE FROM 61% to 96%. Numerous papers suggest that the reason why is due to the inadequate type of immune response generated by the acellular pertussis vaccine versus the previous whole-cell pertussis. Protection against pertussis relies on both humoral immunity and on cellular Th1-type immune responses [3-9]. Seemingly of critical importance are recent studies showing that while the whole-cell pertussis generated a strong antigen-specific Th1 response, aP vaccines induced mixed Th1/Th2 responses in humans [9-12]. It is also important to note that at the time the aP vaccine component was introduced, the technology and know-how did not exist to compare these types of immune responses. However, now that this capability exists and given the apparent failure of the vaccine to illicit long lasting immunity, it seems crucial that public health authorities and vaccine manufacturers address this problem.

Aluminum Adjuvants

While the change in antigen presentation may be sufficient to cause the change in vaccine efficacy, there may be other possible explanations worth exploring as well. The first of these explanations centers on the use of aluminum adjuvants in many vaccines, including DTaP.

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Aluminum has been shown to preferentially generate a Th2-type response [13,14]. In recent years, the use of aluminum adjuvants that induce a strong Th2 response by a mechanism not yet fully understood has increasingly come under criticism by vaccine safety advocates, including Dr. Robert Sears, author of The Vaccine Book. Given the rapid rise of childhood chronic illness, such as allergies and asthma, that are mediated by Th2 responses, this criticism seems warranted and worthy of investigation. The use of adjuvants that stimulate a Th2 response in a vaccine for a disease that requires a Th1 response leads to a less effective vaccine that has a higher safety risk. Of course, back in the late 1980s the need for Th1 response for clearance of pertussis or the tendency of aluminum adjuvants to produce a Th2 response (while suppressing the Th1) was unknown and not yet on the scientific radar. But now these facts are known and are part of the mainstream published scientific literature. To continue this practice as if nothing is wrong is troubling. It is this kind of blindness to scientific fact that is causing concerned citizens to increasingly question the current vaccine paradigm.

Environmental Issues

Furthermore, a recent paper published in the journal Environmental Health Perspectives suggests that the failure of the pertussis vaccine may be the result of our increasingly toxic environment [15]. The study found that postnatal PCB exposure levels had an immunotoxic effect that limited the response to the DTaP vaccine. PCB exposure levels at 18 months of age were most predictive of lowered lasting immune response, including responses below what is considered clinically protective. This is suggestive of a crucial time period during early childhood for the proper development of the immune system. Children with higher PCB levels at age 18 months had a 1.64 odds ratio of not being able to generate clinically protective antibody levels at age seven. It may be that the immune systems of young children are so skewed either from toxic exposure or changes in the development of the immune system generated by the current vaccination schedule that no amount of booster shots with DTaP are going to adequately protect all children. If this is indeed the case, the future of fighting diseases may depend not solely on mass vaccination but rather on finding ways to maintain the proper function and balance of the immune system in this increasingly toxic world.

Regardless of the cause or causes, the increasing failure of the pertussis vaccine requires serious investigation. The unwillingness to honestly inquire about the nature of the failure (presumably because it might cast doubt on the use of aluminum adjuvants, our overall approach to the vaccine program and the safety of grandfathered in products in an ever-changing world) is just another of a long list of examples of the public health authorities refusing to support the vaccine program with adequate research. It is this kind of failure, not Jenny McCarthy, that has parents questioning the logic of the CDC, and many ultimately deciding that the unseen benefits do not outweigh the potential risks.

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References:

[1] Guris D, Strebel P, Bardenheier B, Brennan M, Tachdjian R, Finch E, Wharton M, Livengood J. Changing Epidemeology of Pertussis in the United States: Increasing Reported Incidence Among Adolescents and Adults, 1990-1996. Clin Infect Diseases. 1998. 28: 1230-7.

[2] Centers for Disease Control and Prevention. Pertussis- United States; 2001-2003. Found at www.cdc.gov .

[3] Mills KHG, Barnard A, Watkins J, Redhead K. Cell-mediated immunity to Bordetella pertussis : role of Th1 cells in bacterial clearance in a murine respiratory infection model. Infect Immun 1993; 61(2): 399-410.

[4] Barbic J, Leef MF, Burns DL, Shahin RD. Role of gamma interferon in natural clearance of B ordetella pertussis infection. Infect Immun 1997; 65(12):4904-8.

[5] Redhead K, Watkin J, Barnard A, Mills KHG. Effective immunization against Bordetella pertussis respiratory infection in mice is dependent on induction of cell-mediated immunity. Infect Immun 1993; 61(8):3190-8.

[6] Leef M, Elkins KL, Barbic J, Shahin RD. Protective immunity to Bordetella pertussis requires both B cells and CD4+ T cells for key functions other than specific antibody production. J Exp Med 2000; 191(11):1841-52.

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[7] Ryan M, Murphy G, Gothefors L, Nilsson L, Storsaeter J, Mills KH. Bordetella pertussis respi ratory infection in children associated with preferential activation of type 1 T helper cells. J Infect Dis 1997;175(5): 1246-50.

[8] Mills KHG. Immunity to Bordetella pertussis . Microbes Infect 2001;3(8): 655-77.

[9] Dirix V, Verscheure V, Goetghebuer T, Hainaut M, Debrie A, Locht C, Mascar F. Cytokine and antibody profiles in 1-year-old children vaccinated with either acellular or whole-cell pertussis vaccine during infancy. Vaccine 2009; 27: 6042-47.

[10] Mascart F, Hainaut M, Peltier A, Verscheure V, Levy J, Locht C. Modulation of the infant immune response by the first pertussis vaccine administrations. Vaccine 2007; 25: 391-8.

[11] Ryan M, Murphy G, Ryan E, Nilsson L, Shackley F, Gothefors L et al. Distinct T-cell subtypes induced with whole cell pertussis and acellular pertussis vaccines in children. Immunology 1998; 93: 1-10.

[12] Ausiello CM, Urbani F, la Sala A, Lande R, Cassone A. Vaccine and antigen dependent type 1 and type 2 cytokine induction after primary vaccination of infancts with whole-cell or acellular pertussis vaccines in children. Infect Immun 1997; 65: 2168-74.

[13] Grun JL, Maurer P. Different T helper cell subsets elicited in mice utilizing two different adjuvant vehicles: the role of endogenous interleukin 1 in proliferative responses. Cell Immunol 1989 121: 134-145.

[14] Marrack P, McKee A, Munks M. Towards an understanding of the adjuvant action of aluminum. Nature Immunology. 2009 9: 287-293.

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[15] Heilmann C, Jorgensen E, Nielsen F, Heinzow B, Weihe P, Grandjean P. Serum Concentration of antibodies against vaccine toxoids in children exposed perinatally to immunotoxicants. Environmental Health Perspectives. 2010.

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