ABSTRACT
Background
Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral ...surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID‐19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described.
Methods
Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023.
Results
Prior to widespread circulation of SARS‐CoV‐2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID‐19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era.
Conclusions
Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.
Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited ...cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor.
Highlights • Reintroduction of Variola major as an agent of bioterrorism remains a concern. • A compressed schedule of MVA was evaluated for use in a post event scenario. • MVA is well tolerated when ...given as two standard doses at Days 0 and 28 or 0 and 7. • A 2nd dose of MVA at Day 28 compared to Day 7 provided greater antibody responses. • INF-γ expression was greatest within 2 weeks after last vaccination.
B cells produce a diverse antibody repertoire by undergoing gene rearrangements. Pathogen exposure induces the clonal expansion of B cells expressing antibodies that can bind the infectious agent. To ...assess human B cell responses to trivalent seasonal influenza and monovalent pandemic H1N1 vaccination, we sequenced gene rearrangements encoding the immunoglobulin heavy chain, a major determinant of epitope recognition. The magnitude of B cell clonal expansions correlates with an individual’s secreted antibody response to the vaccine, and the expanded clones are enriched with those expressing influenza-specific monoclonal antibodies. Additionally, B cell responses to pandemic influenza H1N1 vaccination and infection in different people show a prominent family of convergent antibody heavy chain gene rearrangements specific to influenza antigens. These results indicate that microbes can induce specific signatures of immunoglobulin gene rearrangements and that pathogen exposure can potentially be assessed from B cell repertoires.
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•Human antibody gene repertoire sequencing identifies vaccine-specific B cell clones•Quantified B cell clonal expansions correlate with serological vaccine responses•Human pandemic H1N1 2009 influenza vaccine responses show convergent antibodies
Infection stimulates B cells expressing antibodies specific to the pathogen. By sequencing human antibody gene repertoires, Jackson et al. determined that influenza vaccination or infection induces B cell clonal expansions, whose magnitude correlates with individual secreted antibody responses, and that different individuals use convergent antibody rearrangements specific to influenza antigens.
Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine could prevent infant pertussis.
To evaluate the safety and immunogenicity of Tdap ...immunization during pregnancy and its effect on infant responses to diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine.
Phase 1-2, randomized, double-blind, placebo-controlled, clinical trial conducted from 2008 to 2012. Forty-eight pregnant women aged 18 to 45 years received Tdap (n = 33) or placebo (n = 15) at 30 to 32 weeks' gestation, with crossover immunization postpartum.
Tdap vaccination at 30 to 32 weeks' gestation or postpartum.
Primary outcomes were maternal and infant adverse events, pertussis illness, and infant growth and development until age 13 months. Secondary outcomes were antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months' postpartum, and in infants at birth, at 2 months, and after the third and fourth doses of DTaP.
No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 26 (78.8% 95% CI, 61.1%-91.0%) and 12 (80% 95% CI, 51.9%-95.7%) pregnant and postpartum women, respectively (P > .99). Systemic symptoms were reported in 12 (36.4% 95% CI, 20.4%-54.9%) and 11 (73.3% 95% CI, 44.9%-92.2%) pregnant and postpartum women, respectively (P = .03). Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy vs postpartum (eg, pertussis toxin antibodies: 51.0 EU/mL 95% CI, 37.1-70.1 and 9.1 EU/mL 95% CI, 4.6-17.8, respectively; P < .001) and in their infants at birth (68.8 EU/mL 95% CI, 52.1-90.8 and 14.0 EU/mL 95% CI, 7.3-26.9, respectively; P < .001) and at age 2 months (20.6 EU/mL 95% CI, 14.4-29.6 and 5.3 EU/mL 95% CI, 3.0-9.4, respectively; P < .001). Antibody responses in infants born to women receiving Tdap during pregnancy were not different following the fourth dose of DTaP.
This preliminary assessment did not find an increased risk of adverse events among women who received Tdap vaccine during pregnancy or their infants. For secondary outcomes, maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap immunization during pregnancy.
clinicaltrials.gov Identifier: NCT00707148.
Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines ...induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.
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