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Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Departamento de Tocoginecologia, Curso de Medicina, Florianópolis, 199

Simultaneous aerosol and intramuscular immunization with influenza vaccine induces powerful protective local T cell and systemic antibody immune responses in pigs

A vaccine providing both powerful Ab and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. In this study, we evaluated i.m., aerosol (Aer), and simultaneous systemic and respiratory immunization (SIM) by both routes in Babraham pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization, pigs were challenged with H1N1pdm09 virus. i.m.-immunized pigs generated a high titer of neutralizing Abs but poor T cell responses, whereas Aer induced powerful respiratory tract T cell responses but a low titer of Abs. SIM pigs combined high Ab titers and strong local T cell responses. SIM showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study

Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors

Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1–H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model

Are women making informed choices with regard to Combined Ultrasound and Biochemical (CUB) screening in the first trimester of pregnancy?

Background: Previous studies report that women are failing to make informed choices with regard to antenatal screening, due to significant deficits in knowledge. However, current definitions dictate that informed choice occurs not merely as a result of sufficient knowledge, but by acting in line with one’s attitudes despite perceived social pressure (Dormandy et al., 2002). Objective: To investigate whether women are making informed choices with regard to Combined Ultrasound and Biochemical (CUB) screening, using more substantial criteria. Design: Prospective non-experimental. Setting: The Queen Mother’s Maternity Hospital in Glasgow. Sample: 63 women due attend their first antenatal appointment. Outcome measures: responses to a questionnaire constructed for the purposes of the study. Methods: A multidimensional questionnaire measure encompassing demographic factors, areas of knowledge recommended by The Royal College of Obstetricians and Gynaecologists (RCOG, 1993) and all aspects of the Theory of Planned Behaviour (TPB; Ajzen, 1985). Results: Women appeared to be well informed, though there were some worrying misconceptions. Women appeared to intend to act in line with their attitudes, although small numbers of women planning to refuse screening limited findings. Attitude was the strongest predictor of behavioural intention. Conclusions: There appears to be moderate support for the hypothesis that women would make ‘informed choices’, though this is limited by a number of factors which require further investigation

Breaking bad news in assisted reproductive technology : a proposal for guidelines

Background: The issue of breaking bad news in assisted reproductive technology (ART) has been only partially explored by literature, and although some recommendations are available, specific guidelines are lacking. The present study aimed to explore the applicability of the oncologic SPIKES Protocol to the ART context. Methods: Thirteen ART clinicians (7 gynecologists; 4 psychologists; 1 biologist; 1 obstetrician) completed the Critical Incidents Report (CIR) to describe the experience of delivering bad news in ART. The CIRs were first discussed with clinicians, then a focus group was created composed of 13 clinicians, one health communication expert and a patient to discuss the applicability of the six-step (SPIKES) Buckman Protocol to ART. The discussion was audiotaped, transcribed and analyzed with content analysis. Results: The SPIKES Protocol seems to fit ART consultations and participants found it practical and easy to understand. Some specificities were found for the ART context: the reiteration of bad news, the "patient" as a couple and the fact that ability to conceive is closely related to self-esteem, as well as to social and family identity. During the discussion of the SPIKES Protocol, participants highlighted the importance of: 1) providing a caring setting, by adding a reflection on the value of communication by phone; 2) exploring patients perceptions but also misinformation; 3) exploring patients desires and expectations, while balancing the need to be honest and clear; 4) applying Buckmans suggestions for delivering information, and integrating clinical aspects with psychosocial ones; 5) managing and legitimizing patients emotions, in particular anger; 6) having a strategy for follow-up and supporting couples to make meaning of the ART experience. Conclusion: The proposal of a shared protocol for giving bad news in ART could be the starting point for training and experimental studies

Comparison of heterosubtypic protection in ferrets and pigs induced by a single-cycle influenza vaccine

Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication