[Show abstract][Hide abstract] ABSTRACT: The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers.
An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero.
Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)].
All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth).
At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London.
The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60.
Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001).
Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby.
The National Institute for Health Research Health Technology Assessment programme.
[Show abstract][Hide abstract] ABSTRACT: The past 30 years of immunological research have revealed much about the proximate mechanisms of maternal antibody transmission and utilization, but have not adequately addressed how these issues are related to evolutionary and ecological theory. Much remains to be learned about individual differences within a species in maternal antibody transmission as well as differences among species in transmission or utilization of antibodies. Similarly, maternal-effects theory has generally neglected the mechanisms by which mothers influence offspring phenotype. Although the environmental cues that generate maternal effects and the consequent effects for offspring phenotype are often well characterized, the intermediary physiological and developmental steps through which the maternal effect is transmitted are generally unknown. Integration of the proximate mechanisms of maternal antibody transmission with evolutionary theory on maternal effects affords an important opportunity to unite mechanism and process by focusing on the links between genetics, environment and physiology, with the ultimate goal of explaining differences among individuals and species in the transfer of immune function from one generation to the next.
Proceedings of the Royal Society B: Biological Sciences 12/2003; 270(1531):2309-19. DOI:10.1098/rspb.2003.2485 · 5.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Young infants and pregnant women are at increased risk for serious consequences of influenza infection. Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age. We assessed the clinical effectiveness of inactivated influenza vaccine administered during pregnancy in Bangladesh.
In this randomized study, we assigned 340 mothers to receive either inactivated influenza vaccine (influenza-vaccine group) or the 23-valent pneumococcal polysaccharide vaccine (control group). Mothers were interviewed weekly to assess illnesses until 24 weeks after birth. Subjects with febrile respiratory illness were assessed clinically, and ill infants were tested for influenza antigens. We estimated the incidence of illness, incidence rate ratios, and vaccine effectiveness.
Mothers and infants were observed from August 2004 through December 2005. Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85). Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group, with a vaccine effectiveness of 29% (95% CI, 7 to 46). Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57).
Inactivated influenza vaccine reduced proven influenza illness by 63% in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants. Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants. (ClinicalTrials.gov number, NCT00142389.)
New England Journal of Medicine 10/2008; 359(15):1555-64. DOI:10.1056/NEJMoa0708630 · 55.87 Impact Factor
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