Pertactin-Deficient Bordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Longhuan Ma; Amanda Caulfield; Kalyan K. Dewan; Eric T. Harvill


Emerging Infectious Diseases. 2021;27(6):1561-1566. 

In This Article

Persistence of PRN Antibodies

Despite the shortcomings of aP vaccines in generating a strong memory response, and the resulting waning immunity of these vaccines against disease,[39,40] aP vaccines induce robust IgG titers against most of its component antigens. However, this strong humoral response, although protecting against symptoms of pertussis, does not prevent the pathogen from colonizing the upper respiratory tract or from transmitting between hosts.[3] Furthermore, although initially induced at high levels, circulating antibodies decay relatively rapidly across all age groups.[4,40–43] Studies evaluating dynamic levels of specific antibodies across time have consistently show differential rates of decay for the various antigen-specific antibodies, with PT antibody titers decaying more rapidly than antibodies to FHA and PRN (Figure 2). Similarly, FIM2/3 have been reported to poorly stimulate generation of protective antibodies postinfection and postvaccinations,[4,43] although these data conflict with those of other reports that shown higher levels of FIM antibodies, even at 10 years postvaccination. However, the higher antibody titers observed in these reports are also noted to decrease sharply and are likely to reach unprotective levels over a relatively short time. This rapid waning immunity against PT and FIM would be expected to narrow the window of selective pressure against these antigens.

Figure 2.

Differential decay of antibodies against acellular pertussis vaccine antigens and their effective capacity for protection. Antibodies against PRN and FHA remain at relatively higher titers for a longer period. However, PT-specific antibodies decrease to low titers rapidly. A consistently low level of antibodies against FIM is induced. Solid lines indicate antibodies that have high protective capacity, and dotted lines indicate antibodies that had low protective capacity. Only PRN antibodies are highly protective and persist at high titers for years. FHA, filamentous hemagglutinin, FIM, fimbriae; PT, pertussis toxin; PRN, pertactin.

In contrast to antibodies against PT, antibodies against PRN and FHA are relatively more persistent (Figure 2),[38,44,45] suggesting that there is a longer period after vaccination when there are effective titers of antibodies against FHA and PRN. This finding would be expected to result in strong pressure against PRN and FHA. However, in a search for serologic correlates of immunity to pertussis, Le et al.[4] noted that FHA provides relatively little contribution to protection but PRN had a higher protective role.

These observations have recently been validated in studies by Lesne et al., who used human serum bactericidal assays to determine that antibodies to PRN, but no other aP component, are bactericidal in in vitro complement killing assays.[46] These findings somewhat conflict with those of previous studies and testing methods, which often prioritize PT IgG as an indicator for protection against pertussis.[4,45,47] However, the short period during which levels of neutralizing antibodies against PT remain elevated, in contrast to bactericidal antibodies against PRN, suggests that PRN antibodies might be a more appropriate measure for pertussis immunity.

The short period during which antibodies to PT remain at elevated levels indicates that there is a longer period when antibodies to PRN remain at high levels, but levels of antibodies to PT have decreased. Le et al. also noted that a much larger proportion of enrolled patients tested before aP vaccination already had high titers of antibodies to PRN, and many had antibodies to PT.[4] Therefore, in addition to its surface localization and strong opsonizing potential, the persistence of the PRN antibodies is likely to contribute to prolonged selection against this antigen in particular.