Waning Immunity and Microbial Vaccines—Workshop of the National Institute of Allergy and Infectious Diseases

Gu, Xin-Xing; Plotkin, Stanley А.; Edwards, Kathryn M.; Sette, Alessandro; Mills, Kingston H. G.; Levy, Ofer; Sant, Andrea J.; Mo, Annie X.; Alexander, William; Lu, Kristina T.; Taylor, Christopher E.

doi:10.1128/cvi.00034-17

Cited by 40 publications

(31 citation statements)

References 86 publications

(78 reference statements)

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“…The recent resurgence of pertussis is particularly associated with children aged 6 to 11 years or adolescents and young adults and has been linked to the waning of pertussis-specific immunity, despite the addition of a booster vaccination with the aP vaccine in this age bracket (15,(36)(37)(38)(39)(40). It would thus appear that a key difference or differences exist in pertussis immunity as a function of the original childhood vaccination with aP compared with wP.…”

Section: Resultsmentioning

confidence: 99%

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

Antunes¹,

Babor²,

Carpenter³

et al. 2018

Journal of Clinical Investigation

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109

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In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-β and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.

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Section: Resultsmentioning

confidence: 99%

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

Antunes¹,

Babor²,

Carpenter³

et al. 2018

Journal of Clinical Investigation

Self Cite

109

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“…Modifying MMR vaccines to improve the magnitude or duration of immune responses against mumps virus may also improve protection. Notably, the mumps component of the vaccine induces lower-avidity antibody responses, and weaker specific memory B-cell proliferation, than the measles and rubella components (37, 38). …”

Section: Discussionmentioning

confidence: 99%

Vaccine waning and mumps re-emergence in the United States

2018

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Following decades of declining mumps incidence amid widespread vaccination, the United States and other developed countries have experienced a resurgence in mumps cases over the last decade. Outbreaks affecting vaccinated individuals and communities with high vaccine coverage have prompted concerns about the effectiveness of the live attenuated vaccine currently in use. It is unclear if immune protection wanes, or if the vaccine protects inadequately against currently circulating mumps virus lineages. Synthesizing data from six studies of mumps vaccine effectiveness, we estimated that vaccine-derived immune protection against mumps wanes on average 27 (95% confidence interval: 16 to 51) years post-vaccination. After accounting for this waning, we found no evidence that the emergence of heterologous virus genotypes contributed to changes in vaccine effectiveness over time. A mathematical model of mumps transmission confirmed the central role of waning immunity to the vaccine in the re-emergence of mumps cases. Outbreaks from 2006 to the present among young adults, and outbreaks in the late 1980s and early 1990s among adolescents, aligned with peaks in mumps susceptibility of these age groups predicted to be due to loss of vaccine-derived protection. In contrast, evolution of mumps virus strains escaping immune pressure would be expected to cause a higher proportion of cases among children, not adolescents and young adults as observed. Routine use of a third vaccine dose at age 18 years, or booster dosing throughout adulthood, may be a strategy to prevent mumps re-emergence and should be assessed in clinical trials.

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“…Whether this observation also holds true for birth doses requires future study. Given current concerns of waning immunity to aP ( 48 ), novel pertussis vaccine formulations, potentially including developing pertussis vaccines that are safe and effective in newborns, are needed to induce robust and durable immunity against this pathogen.…”

Section: Clinical Studies Of Other Vaccines At Birthmentioning

confidence: 99%

Neonatal Immunization: Rationale, Current State, and Future Prospects

2018

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Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a distinct neonatal immune system that is generally polarized against Th1 responses to many stimuli such that some vaccines that are effective in adults are not in newborns. Nevertheless, neonatal immunization could result in high-population penetration as birth is a reliable point of healthcare contact, and offers an opportunity for early protection of the young, including preterm newborns who are deficient in maternal antibodies. Despite distinct immunity and reduced responses to some vaccines, several vaccines have proven safe and effective at birth. While some vaccines such as polysaccharide vaccines have little effectiveness at birth, hepatitis B vaccine can prime at birth and requires multiple doses to achieve protection, whereas the live-attenuated Bacille Calmette–Guérin (BCG), may offer single shot protection, potentially in part via heterologous (“non-specific”) beneficial effects. Additional vaccines have been studied at birth including those directed against pertussis, pneumococcus, Haemophilus influenza type B and rotavirus providing important lessons. Current areas of research in neonatal vaccinology include characterization of early life immune ontogeny, heterogeneity in and heterologous effects of BCG vaccine formulations, applying systems biology and systems serology, in vitro platforms that model age-specific human immunity and discovery and development of novel age-specific adjuvantation systems. These approaches may inform, de-risk, and accelerate development of novel vaccines for use in early life. Key stakeholders, including the general public, should be engaged in assessing the opportunities and challenges inherent to neonatal immunization.

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Waning Immunity and Microbial Vaccines—Workshop of the National Institute of Allergy and Infectious Diseases

Cited by 40 publications

References 86 publications

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

Vaccine waning and mumps re-emergence in the United States

Neonatal Immunization: Rationale, Current State, and Future Prospects

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