pertussis vaccine -- not quite up to snuff

i've commented in a few blogs about the resurgence of pertussis, despite immunizing adults with the Tdap. i thought it might be useful to elaborate -- there have been a few insights into what seems to be happening.

--in the bad old days, pertussis infection was pretty rampant in the US

--with the development of the whole inactivated  pertussis vaccine in the 1940s, the number of cases plummeted from 157/100K to 1/100K in 1973.

--there have been gradual increases in pertussis since 1982, attributed to the fact that immunity from pertussis is not life-long, as for example, it is with measles. in 2012 there were 42,000 cases in the US. some of this is undoubtedly ascertainment bias: for example, a study of adolescents/adults with prolonged cough actually looked at it and found that 13-20% had b. pertussis infection (see Clin Microbiol Rev 2005; 18: 326). also, newer studies are using PCR and finding much more b. pertussis overall than previously.

--because of adverse effects (esp high fevers, with about 1 in 330 kids getting temperatures > 105 deg, and about 1/2 getting temps >100.4 --  by the way, these were treatable with acetaminophen, and we used to suggest giving the kid acetaminophen prior to the vaccine, which used to prevent many of the complications), an acellular vaccine was developed in the 1990s based on pieces of the b. pertussis bacterium, renaming the old DPT as DTaP, and was used exclusively in kids (the "a" was for acellular).

--however, it became clear that the immunogenicity of the acellular pertussis component was not as strong as the older inactivated pertussis vaccine (see, for example, NEJM 2012; 367: 785). A California study looked at kids who received their fifth/final dose of DTaP from 2006-2011, a time-span which included the large pertussis outbreak in 2010. they looked at 277 kids who developed pertussis (PCR positive) vs 3318 PCR-negative controls and determined when they received their last DTaP vaccine, finding that those who developed PCR-positive pertussis were more likely to receive their DTaP earlier, with an odds of acquiring pertussis increasing 42% per year (see pertussis waning protection nejm 2012 in dropbox, or  NEJM 2012; 367: 1012).

--as pertussis infections became more common, the CDC  recommended adults be vaccinated with the acellular vaccine (Tdap) once, though we are now experiencing pertussis outbreaks in adults within a few years after this vaccine was administered (making the suggestion of one vaccine in one's adult life a tad suspect). 

--infant baboons were infected with b. pertussis bacteria at age 7 months, with 2 groups having been vaccinated before (with either acellular or whole-cell pertussis vaccines at ages 2, 4,and 6 months), a group naive to infection and unvaccinated, and another group who had prior infection. results: colonization of the nasopharynx was no different in those who were unvaccinated and naive to infection and those immunized with the acellular vaccine (there was a gradual decrease in colonization after 14 days, cleared by 30 days). there was dramatically less colonization in those given whole-cell vaccine (almost all cleared by 14 days). and there was no colonization in those previously infected. those with nasopharyngeal colonization after acellular vaccine were able to transmit pertussis infection to naive animals.

Also, they found that the actual immunologic T-cell response of those given the whole-cell vaccine was the same as seen in baboons who had natural infection, whereas the acellular vaccine produced a significantly different immunologic response (see pertussis acellular not prevent transmission PNAS 2015 in dropbox, or doi/10.1073/pnas.1314688110).

--so, let's see: we have a serious infection which does not create life-long immunity, an old vaccine that really worked well but had too many adverse effects, a new vaccine which not only does not elicit the same immunologic response as the natural infection but seems to work only transiently and probably does not do much to affect colonization or potential transmission..... About time to develop a more effective pertussis vaccine????