Seasonal trivalent influenza vaccination during pregnancy and the incidence of stillbirth: population-based retrospective cohort study

Concern for the safety to the fetus is a commonly cited reason for vaccine refusal during pregnancy. Results from this investigation support the safety of seasonal influenza vaccination during pregnancy and suggest seasonal influenza vaccination may be protective against stillbirth

A prospective cohort study comparing the reactogenicity of trivalent influenza vaccine in pregnant and non-pregnant women

Background: Influenza vaccination during pregnancy can prevent serious illness in expectant mothers and provide protection to newborns; however, historically uptake has been limited due to a number of factors, including safety concerns. Symptomatic complaints are common during pregnancy and may be mistakenly associated with reactions to trivalent influenza vaccine (TIV). To investigate this, we compared post-vaccination events self-reported by pregnant women to events reported by non-pregnant women receiving TIV. Methods: A prospective cohort of 1,086 pregnant women and 314 non-pregnant female healthcare workers (HCWs) who received TIV between March-May 2014 were followed-up seven days post-vaccination to assess local and systemic adverse events following immunisation (AEFIs). Women were surveyed by text message regarding perceived reactions to TIV. Those reporting an AEFI completed an interview by telephone or mobile phone to ascertain details. Logistic regression models adjusting for age and residence were used to compare reactions reported by pregnant women and non-pregnant HCWs. Results: Similar proportions of pregnant women and non-pregnant, female HCWs reported ≥1 reaction following vaccination with TIV (13.0% and 17.3%, respectively; OR = 1.2 [95% CI: 0.8-1.8]). Non-pregnant, female HCWs were more likely to report fever or headache compared to pregnant women (OR: 4.6 [95% CI 2.1-10.3] and OR: 2.2 [95% CI 1.0-4.6], respectively). No other significant differences in reported symptoms were observed. No serious vaccine-associated adverse events were reported, and less than 2% of each group sought medical advice for a reaction. Conclusions: We found no evidence suggesting pregnant women are more likely to report adverse events following influenza vaccination when compared to non-pregnant female HCWs of similar age, and in some cases, pregnant women reported significantly fewer adverse events. These results further support the safety of TIV administered in pregnant women

An Economical Tandem Multiplex Real-Time PCR Technique for the Detection of a Comprehensive Range of Respiratory Pathogens

This study used real-time PCR assays to screen small sample volumes for a comprehensive range of 35 respiratory pathogens. Initial thermocycling was limited to 20 cycles to avoid competition for reagents, followed by a secondary real-time multiplex PCR. Supplementary semi-nested human metapneumovirus and picornavirus PCR assays were required to complete the acute respiratory pathogen profile. Potential pathogens were detected in 85 (70%) of pernasal aspirates collected from 121 children with acute respiratory symptoms. Multiple pathogens were detected in 29 (24%) of those samples. The tandem multiplex real-time PCR was an efficient method for the rapid detection of multiple pathogens

Innate immunity defines the capacity of antiviral T cells to limit persistent infection

Effective immunity requires the coordinated activation of innate and adaptive immune responses. Natural killer (NK) cells are central innate immune effectors, but can also affect the generation of acquired immune responses to viruses and malignancies. How NK cells influence the efficacy of adaptive immunity, however, is poorly understood. Here, we show that NK cells negatively regulate the duration and effectiveness of virus-specific CD4+ and CD8+ T cell responses by limiting exposure of T cells to infected antigen-presenting cells. This impacts the quality of T cell responses and the ability to limit viral persistence. Our studies provide unexpected insights into novel interplays between innate and adaptive immune effectors, and define the critical requirements for efficient control of viral persistence

Protection against murine cytomegalovirus infection by passive transfer of neutralizing and non-neutralizing monoclonal antibodies

The ability of eight neutralizing monoclonal antibodies (MAbs) specific for structural proteins of murine cytomegalovirus (MCMV) to protect mice passively against MCMV infection was examined to determine firstly whether a correlation existed between the neutralization titres of the MAbs in vitro and the protection afforded by the MAbs in vivo and, secondly, the contribution of the host towards neutralization by the MAbs in vivo. The reduction in MCMV titre in the livers of BALB/c and C57BL/10 mice by the MAbs closely correlated with their neutralization titres in vitro. However, in the spleens of BALB/c mice, in which MCMV replicates to high titre, almost all of the MAbs tested were ineffective in reducing MCMV replication. Indeed, a significant increase in splenic MCMV replication was observed in mice treated 24 h prior to MCMV replication with either neutralizing MAbs or polyclonal Ig. Each of six MAbs prophylacti-cally protected between 66 and 100 % of mice from an intraperitoneal challenge with 4 LDs0 MCMV regardless of their neutralization titre in vitro. The persistence of MCMV replication in the salivary gland was not prevented by either polyelonal Ig or MAbs. Despite the absolute requirement for complement for the neutralization of MCMV in vitro, both polyclonal lg and MAb 4F9 protected A/J mice, which are deficient in the fifth component of complement, as efficiently as they did complement competent BALB/c mice. These results demonstrate that MAbs specific for single MCMV polypeptides are protective in vivo. In addition, the extent to which the MAbs protected against MCMV could not be predicted from their immunoreactive or neutralizing titres in vitro or by their effect on splenic MCMV replication in vivo. Furthermore, these studies suggest that the mechanism(s) of neutralization of MCMV in vitro are different to those which act in vivo

Innate resistance to flavivirus infection in mice controlled by Flv is nitric oxide-independent

Innate resistance to flaviviruses in mice is active in the brain where it restricts virus replication. This resistance is controlled by a single genetic locus, Flv, located on mouse chromosome 5 near the locus encoding the neuronal form of nitric oxide synthase (Nos1). Since nitric oxide (NO) has been implicated in antiviral activity, its involvement in natural resistance to flaviviruses has been hypothesized. Here we present data on NO production before and during flavivirus infection in both brain tissue and peritoneal macrophages from two flavivirus-resistant (Flv r) and one congenic susceptible (Flv s) mouse strains. This study provides evidence that NO is not involved in the expression of flavivirus resistance controlled by Flv since: (a) there is no difference in brain tissue NO levels between susceptible and resistant mice, and (b) lipopolysaccharide-induced NO does not abrogate the difference in flavivirus replication in peritoneal macrophages from susceptible and resistant mice.</jats:p

Using record linkage to demonstrate the benefits of maternal influenza immunisation in Western Australia

ABSTRACT Objectives Pregnant women are the highest priority for seasonal influenza vaccination. Previous research has found maternal immunisation may not only reduce respiratory infections in mothers and infants, but also prevents adverse birth outcomes. Although the vaccine has been offered to pregnant women under the National Immunisation Program since 2009, no population-based study has yet evaluated its impact on neonatal health in Australia. Approach We established a large retrospective cohort of 58,615 births between 2012 and 2013 in Western Australia using data linkage of state-held maternal vaccination records, birth registrations, hospital inpatient records, and midwives notifications. Cox regression models were used to compare the adjusted relative hazard (HR) of adverse birth outcomes and hospital admission for an acute respiratory illness (ARI) by vaccination status. Results In total, 5,241 (8.9%) of infants were born to vaccinated mothers. Between 2012 and 2013, there were 23.6 ARI admissions per 1,000 infants <6 months and 2.8 ARI admissions per 1,000 pregnant women. Influenza vaccination was associated with a 51% reduction in stillbirth (aHR: 0.49; 95% CI: 0.29-0.84) and a 25% reduction in infant admissions in the first six months of life (aHR: 0.75; 95% CI: 0.56-0.99). Most of the reduction in ARI admission in infants was observed when vaccination occurred in the third trimester (aHR: 0.68; 95% CI: 0.47-0.95). Conclusions Our findings support the neonatal health benefits afforded by maternal influenza immunisation and underscore the importance of offering and promoting influenza vaccination to pregnant women. Considering more than 90% of women who choose to be immunised do so to protect their infant, these results could be used to powerfully promote maternal immunisation