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The question is on the right track but not complete. To complete it we need to add, ‘as well as it used to‘.

The addendum implies two things, one, pertussis vaccine changed over the years, and two, the change made it less protective. There is data to support both these assertions.

First, some basics

  • Pertussis or whooping cough is usually caused by the bacterium Bordetella pertussis (B. pertussis).
  • It spreads through airborne droplets expelled by the infected person during coughs and sneezes.

Two, pertussis vaccine changed over the years. How and why?

  1. Developed during the 1930s, the original pertussis vaccine was simply killed B. pertussis bacteria, given as a combo vaccine, DTwP (Diphtheria toxoid-Tetanus toxoid-[killed/whole] Pertussis).
  2. The wP in DTwP was erroneously blamed for side effects such as encephalopathy-associated seizures and subsequent intellectual disability. In the 1980s, some parents successfully sued vaccine manufacturers for harming their children. The two-fold result was fewer pertussis vaccine manufacturers as many left the field, and urgent search for safer alternatives.
  3. B. pertussis cell wall component, endotoxin, was implicated in the side-effects.This suggested an apparently easy solution, remove this cell wall component and we’d have a safer pertussis vaccine.
  4. In the 1990s, developed countries including US switched to the newer DTaP (Diphtheria toxoid-Tetanus toxoid-[acellular] Pertussis)), which contains purified pertussis antigens (proteins) without the endotoxin.
  5. Early comparisons of DTwP versus DTaP reassured, using two parameters then considered most important.

a) DTwP and DTaP stimulated comparable circulating antibody titers.
b) DTaP much safer compared to DTwP, i.e. hardly any or fewer adverse responses.

Three, consequence of pertussis vaccine change

  1. Certainly looked as though vaccinologists had achieved the impossible, i.e., increased vaccine safety (less reactogenicity) while retaining similar effectiveness (similar immunogenicity).
  2. It’s taken almost two decades to understand that immunity is not so easily deceived. A safer vaccine does not induce similarly effective immunity.
  3. In particular, immunity induced by DTaP wanes rapidly as seen by rising cases since the mid-1990s switch from DTwP to DTaP. This even with effective vaccine coverage of the population.
  4. The aP in DTaP is clearly not as effective in protecting against pertussis as the wP in DTwP. However, we are more risk-averse today than in the infancy of the vaccine era so going back to DTwP seems an unrealistic option.

From 1

Key lessons learned since the DTwP to DTaP change

  1. Inducing effective protective immunity is not cost-free. Such immunity is long-lasting, i.e. generates robust immunological memory. We don’t understand yet what’s necessary for robust immunological memory, and certainly we didn’t appreciate this at all when we switched from DTwP to DTaP. However, we do know now that we need the initial punch from materials like endotoxin, materials that cause some local damage and induce physiological responses like fever. When it comes to long-lasting protective immunity, the ‘no pain, no gain’ truism applies.
  2. The connection between DTwP and febrile seizures turned out to be ill-founded. Recent studies (2) including a retrospective 2010 analysis (3) showed the children who developed febrile seizures had de-novo mutations in the sodium channel gene SCN1A (Dravet Syndrome). This analysis showed that DTwP post-first seizure did not influence outcome of syndrome. If vaccine played a role, surely syndrome should have worsened. Yet children who got DTwP before or after their first seizure had similar clinical outcome, including cognitive disability. The underlying SCN1A mutation likely caused seizures, and confirmation bias likely implicated DTwP vaccine in the original studies. Caveats to this analysis are usual ones attendant to such retrospective analyses, namely, reliance on previously recorded clinical data, small numbers, lack of unvaccinated control group. However, these caveats do not overturn the link between SCN1A mutation (Dravet Syndrome) and febrile seizure.

Gaps in current pertussis knowledge and confounding factors

  1. What is effective anti-pertussis immunity? Still unknown. Relevant and irrelevant anti-pertussis immune responses are indistinguishable by current methods. Why? Because there is no functional assay, one that would show immune response x and not y killed B. pertussis and/or that it prevented infected to uninfected transmission. Lack of such functional assays led to erroneous conclusions in the 1980s and 1990s that DTwP and DTaP induced equivalent immunity. After all, antibody titers against the two were equivalent, right? Two decades of increasing pertussis cases even with effective DTaP coverage proved that DTwP, and not DTaP, better protected against disease and better prevented disease transmission (herd immunity). There was, and still is, no method to distinguish effective and ineffective human anti-pertussis immune responses. Human anti-pertussis T cell responses in particular are poorly understood.
  2. How well do current or experimental pertussis vaccines really protect, i.e. what’s the vaccine efficacy? Wrong to assume this would be well-understood by now. Why? In 1991, the WHO developed the still-current pertussis case definition as ‘laboratory confirmation and >21 days of paroxysmal cough‘. In retrospect, this too-conservative pertussis case definition likely padded vaccine efficacy by missing/eliminating a good number of cases. In other words, DTaP was likely never as good at preventing pertussis disease and transmission as originally assumed.
  3. Lack of predictive animal models. Earlier studies used macaque monkeys. 2012 data suggest baboons may better reflect human anti-pertussis immunity (4).
  4. What are necessary and essential B. pertussis components in a vaccine that would induce long-lasting protective anti-pertussis immunity? No consensus yet.
  5. To complicate matters further, since 2009 (5), B. pertussis strains that have lost or varied some of the key proteins used in the vaccines, proteins such as pertactin (loss) and pertussis toxin (mutated), are increasingly showing up in infected populations in Australia, Canada, Finland, France, US. Is the less effective DTaP driving such B.pertussis loss variants in the population, i.e. maybe DTaP drives not just ineffectual immunity but also one that selects for much more efficiently transmitted strains? Should newer vaccines account for such changes and cover the mutated protein as well?
  6. More sensitive diagnostic methods show that other Bordetella such as B. holmesii and B. parapertussis also cause pertussis. Could DTaP cross-protect? Did DTwP cross-protect? Open questions.
  7. What’s the most appropriate vaccine route of administration? This is an issue that experts routinely gloss over. Many vaccines including pertussis are given intramuscularly. As I’ve written elsewhere*, ‘since over evolutionary time, infections honed their preferred routes, their typical “portals of entry“, it stands to reason that the sequence of events surrounding their entry would be a well orchestrated sequential dance that likely influences the nature and strength of the ensuing immunity, much of which is likely circumvented by a typical vaccine‘s route of administration’.
  8. Argument against point 7 is that DTwP was effective even as an intramuscular injection. However, given that a product with DTwP-like safety profile is unlikely to get approved for human use today, and that such unrealistic safety-first stance demands the seeming impossible, namely long-lasting protective immunity (gain) without reactions (pain), routes of administration absolutely need to be re-considered since the onus is that newer vaccine candidates have a better safety profile compared to DTwP. That being the case, mimicking the natural route of infection (nasal and/or oral) might offer the necessary advantage to get over the inbuilt drawback of weaker immunogenicity (capacity to drive immune responses) of such safer vaccines.

* Tirumalai Kamala’s answer to Immunology: Why does the immune system “forget” acquired immunity, and why does the rate of “forgetting” differ among infections?

Bottomline, the public needs to have more realistic expectations of vaccine risks, and scientists/physicians/vaccinologists need to be more transparent in clearly articulating the trade-off between vaccine safety and efficacy, namely, that a very safe vaccine is likely to be less effective.

Bibliography

  1. Allen, Arthur. “The Pertussis Paradox.” Science 341.6145 (2013): 454-455. Page on mtsac.edu
  2. Berkovic, Samuel F., et al. “De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study.” The Lancet Neurology 5.6 (2006): 488-492. http://dravet.is/fs/Fr%C3%83%C2%A6%C3%83%C2%B0igreinar/De-novo%20mutations%20of%20the%20sodium%20channel%20gene%20SCN2A%20in%20alleged%20vaccine%20encephalopathy%20a%20retrospective%20study.pdf
  3. McIntosh, Anne M., et al. “Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study.” The Lancet Neurology 9.6 (2010): 592-598. Page on els-cdn.com
  4. Warfel, Jason M., et al. “Nonhuman primate model of pertussis.” Infection and immunity 80.4 (2012): 1530-1536. Nonhuman Primate Model of Pertussis
  5. Bouchez, V., et al. “First report and detailed characterization of B. pertussis isolates not expressing pertussis toxin or pertactin.” Vaccine 27.43 (2009): 6034-6041.

https://www.quora.com/Why-is-the-pertussis-vaccine-not-protecting-those-vaccinated-for-pertussis/answer/Tirumalai-Kamala

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