Long-term analysis of pertussis vaccine immunity uncovers a memory B cell response to whole cell pertussis immunization that is absent from acellular immunized mice

Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the longest murine pertussis vaccine studies to date, spanning out to 532 days post primary immunization. Vaccine-induced memory results from follicular responses and germinal center formation; therefore, cell populations and cytokines involved with memory were measured alongside protection from challenge. Both aP and wP immunization elicit protection from intranasal challenge and generation of pertussis specific antibody responses in mice. Responses to wP vaccination were characterized by a significant increase in T follicular helper cells in the draining lymph nodes and CXCL13 levels in sera compared to aP mice. In addition, a population of B. pertussis + memory B cells was found to be unique to wP vaccinated mice. This population peaked post-boost, and was measurable out to day 365 post-vaccination. Anti- B. pertussis and anti-pertussis toxoid antibody secreting cells increased one day after boost and remained high at day 532. The data suggest that follicular responses, and in particular CXCL13 levels in sera, should be monitored in pre-clinical and clinical studies for the development of the next-generation pertussis vaccines.

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Effectiveness of a third dose of BNT162b2 or mRNA-1273 vaccine for preventing post-vaccination COVID-19 infection: an observational study

10.1101/2021.11.29.21266777 ◽

2021 ◽

Author(s):

Aditya Sharma ◽

Gina Oda ◽

Mark Holodniy

Keyword(s):

Incidence Rate Ratio ◽

Veterans Health Administration ◽

Veterans Health ◽

Health Administration ◽

Term Care ◽

Post Vaccination ◽

Primary Series ◽

Waning Immunity ◽

Hispanic White

Background BNT162b2 and mRNA-1273 vaccines are highly protective against COVID-19. Concern about waning immunity and reduced effectiveness against SARS-COV-2 variants led to use of a third dose six months after completing the primary series. We used data from the Veterans Health Administration to evaluate the effectiveness of a third dose of BNT162b2 or mRNA-1273 compared to the primary series in preventing post-vaccination COVID-19. Methods During January 1 - November 22, 2020, third dose recipients were matched (1:1) to demographically similar controls who did not receive a third dose. Eligible participants had completed the primary series at least six months (180 days) before recruitment date. Long-term care residents were excluded. Primary outcomes were documented SARS-CoV-2 infection and COVID-19 hospitalization. Effectiveness was estimated as 1-incidence rate ratio. Findings Following matching, the BNT162b2 group included 99,856 pairs and the mRNA-1273 group included 74,116 pairs. In BNT162b2 and mRNA-1273 groups, median age was 72 (interquartile range [IQR]: 65-75) and 72 (IQR: 67-76) years, 94,990 (95.1%) and 71,213 (96.1%) were male, and 61,261 (61.3%) and 52,170 (70.4%) were non-Hispanic White, respectively. Effectiveness of a third dose of BNT162b2 or mRNA-1273 compared to the primary series was 49.4% (95% confidence interval [CI]: 41.2-56.5%) and 46.0% (95% CI: 33.5-56.2%) for documented SARS-CoV-2 infection and 52.3% (95% CI: 33.8-65.6%) and 44.7% (95% CI: 10.7-65.7%) for COVID-19 hospitalization, respectively. Interpretation A third dose of BNT162b2 or mRNA-1273 is moderately effective against post-vaccination COVID-19 infection compared to the primary series.

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