Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus-diphtheria-acellular pertussis vaccine: a randomised, double-blind, phase 2b trial.

BACKGROUND: Bordetella pertussis epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussis infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus-diphtheria-acellular pertussis vaccine (Tdap). METHODS: In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18-50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one B pertussis antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT03942406. FINDINGS: Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1-BPZE1 group, 92 to the BPZE1-placebo group, 46 to the Tdap-BPZE1 group, and 50 to the Tdap-placebo group. Seroconversion of at least one B pertussis-specific nasal secretory IgA was recorded in 79 (94% [95% CI 87-98]) of 84 participants in the BPZE1-BPZE1 group, 89 (95% [88-98]) of 94 in the BPZE1-placebo group, 38 (90% [77-97]) of 42 in the Tdap-BPZE1 group, and 42 (93% [82-99]) of 45 in the Tdap-placebo group. BPZE1 induced broad and consistent B pertussis-specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination. INTERPRETATION: BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert B pertussis infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials. FUNDING: ILiAD Biotechnologies.

Humoral Immunogenicity of the mRNA-1273 Vaccine in the Phase 3 Coronavirus Efficacy (COVE) Trial.

BACKGROUND: Messenger RNA (mRNA)-1273 vaccine demonstrated 93.2% efficacy against coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial. The humoral immunogenicity results are now reported. METHODS: Participants received 2 mRNA-1273 (100 µg) or placebo injections, 28 days apart. Immune responses were evaluated in a prespecified, randomly selected per-protocol immunogenicity population (n = 272 placebo; n = 1185 mRNA-1273). Serum binding antibodies (bAbs) and neutralizing antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike protein were assessed at days 1, 29, and 57 by baseline SARS-CoV-2-negative (n = 1197) and SARS-CoV-2-positive (n = 260) status, age, and sex. RESULTS: SARS-CoV-2-negative vaccinees had bAb geometric mean AU/mL levels of 35 753 at day 29 that increased to 316 448 at day 57 and nAb inhibitory dilution 50% titers of 55 at day 29 that rose to 1081 at day 57. In SARS-CoV-2-positive vacinees, the first mRNA-1273 injection elicited bAb and nAb levels that were 11-fold (410 049) and 27-fold (1479) higher than in SARS-CoV-2-negative vaccinees, respectively, and were comparable to levels after 2 injections in uninfected participants. Findings were generally consistent by age and sex. CONCLUSIONS: mRNA-1273 elicited robust serologic immune responses across age, sex, and SARS-CoV-2 status, consistent with its high COVID-19 efficacy. Higher immune responses in those previously infected support a booster-type effect. Clinical Trials Registration. NCT04470427.

Long-term neurological outcomes in West Nile virus-infected patients: an observational study.

The Houston West Nile Cohort (HWNC) was founded in 2002 when West Nile virus (WNV) reached Houston, TX. The long-term outcomes following WNV infection are still mostly unknown, though neurological abnormalities up to 1 year postinfection have been documented. We report an observational study of neurological abnormalities at 1-3 and 8-11 years following WNV infection in the HWNC. We conducted standard neurological examinations at two separate time points to assess changes in neurological status over time. The majority of patients (86%, 30/35) with encephalitis had abnormal neurological exam findings at the time of the first assessment compared with uncomplicated fever (27%, 3/11) and meningitis (36%, 5/14) cases. At the time of the second assessment, 57% (4/7) of West Nile fever (WNF), 33% (2/6) of West Nile meningitis (WNM), and 36% (5/14) of West Nile encephalitis (WNE) had developed new neurological complications. The most common abnormalities noted were tandem gait, hearing loss, abnormal reflexes, and muscle weakness. Long-term neurological abnormalities were most commonly found in patients who experienced primary WNV encephalitis. New abnormalities may develop over time regardless of initial clinical infection. Future studies should aim to differentiate neurological consequences due to WNV neuroinvasive infection versus neurological decline related to comorbid conditions.