An oligonucleotide, encoding a short epitope peptide tag, termed Pk, was inserted at the 3'-end of the gene coding B-subunit of Escherichia coli heat-labile enterotoxin (LTB). The presence of the Pk epitope on LTB-PK was used to construct novel macromolecular assemblies comprising LTB-Pk, an anti-Pk mAb, (mAb SV5-P-k) and Pk-linked recombinant SIV proteins. The 1:1:1 stoichiometry of such complexes was ensured by binding LTB-Pk to one ann of mAb SVS-P-k and an SIV-Pk antigen to the other arm of the antibody. Such SIV-mAb-LTB macromolecular complexes bound to GM1-ganglioside in vitro, and when immunized systemically into mice were highly immunogenic, inducing both humoral and cell-mediated responses to the recombinant SIV antigens.
Background: Due to an increased risk of sexually transmitted infections (STIs), gay, bisexual and other men who have sex with men (MSM) have been recommended to receive vaccinations against human papillomavirus, meningitis C and hepatitis A/B. This review aimed to compare the rates of vaccine accept ability, uptake and completion, and to identify determinants of vaccine outcomes specific to MSM to inform a theoretical framework.
Methods: In January 2020 four databases were explored to identify vaccination behaviours and associ ated factors among MSM. A narrative systematic review and meta-analysis were performed. Data were synthesised for theoretical modelling.
Results: Seventy-eight studies, mostly from the USA, were included. The average vaccine acceptability was 63% (median = 72%, range: 30%-97%), vaccine uptake 45% (median = 42%, range: 5%-100%) and vac cine completion 47% (median = 45%, range: 12%-89%). Six categories of factors associated with vaccina tion acceptability, uptake and completion were conceptualised: Individual (e.g., demographic and psychosocial); Interpersonal (e.g., peer education); Healthcare provider (e.g., vaccine recommendation); Organisational and practice setting (e.g., routine collection of patient sexual orientation information that is integrated into a clinical decision support system); Community environment (e.g., targeted health pro motion campaigns); and National, state and local policy environment (e.g., public health guidelines tar geting MSM).
Conclusion: Despite overall high levels of acceptability, uptake and completion rates were below targets predicted by cost-effectiveness modelling across all recommended vaccines. These parameters may need to be adjusted for more precise estimations of cost-effectiveness. Addressing the multiple levels of deter minants, as outlined in our theoretical framework, will help guide interventions to increase vaccine com pletion among MSM.
Neutralizing antibodies play an essential part in antiviral immunity and are instrumental in preventing or modulating viral diseases. Polyclonal antibody preparations are increasingly being replaced by highly potent monoclonal antibodies (mAbs). Cocktails of mAbs and bispecific constructs can be used to simultaneously target multiple viral epitopes and to overcome issues of neutralization escape. Advances in antibody engineering have led to a large array of novel mAb formats, while deeper insight into the biology of several viruses and increasing knowledge of their neutralizing epitopes has extended the list of potential targets. In addition, progress in developing inexpensive production platforms will make antiviral mAbs more widely available and affordable.
Background: Men who have sex with men (MSM) are recommended the Human Papillomavirus (HPV) vaccination due to their higher risk of genital warts and anal cancer. Purpose: To examine HPV vaccine acceptability amongst MSM in the UK. Methods: Using advertisements via Facebook, MSM were recruited to an online survey measuring motivations for HPV vaccination. Logistic regression was performed to identify predictors of HPV vaccine acceptability. Results: Out of 1508 MSM (median age = 22, range: 14–63 years) only 19% had good knowledge of HPV. Overall, 55% of MSM were willing to ask for the HPV vaccine and 89% would accept it if offered by a healthcare professional (HCP). Access to sexual health clinics (SHCs) [OR = 1.82, 95% CI 1.29–2.89], the disclosure of sexual orientation to a HCP [OR = 2.02, CI 1.39–3.14] and HIV-positive status [OR = 1.96, CI 1.09–3.53] positively predicted HPV vaccine acceptability. After receiving information about HPV, perceptions of HPV risk [OR = 1.31, CI 1.05–1.63], HPV infection severity [OR = 1.89, CI 1.16–3.01), HPV vaccination benefits [OR = 1.61, CI 1.14–3.01], HPV vaccine effectiveness [OR = 1.54, CI 1.14–2.08], and the lack of perceived barriers to HPV vaccination [OR = 4.46, CI 2.95–6.73] were also associated with acceptability. Conclusions: Although nearly half of MSM would not actively pursue HPV vaccination, the vast majority would accept the vaccine if recommended by HCPs. In order to achieve optimal uptake, vaccine promotion campaigns should focus on MSM who do not access SHCs and those unwilling to disclose their sexual orientation.
We assessed the direct and indirect economic costs and benefits of the current policy of revaccinating tuberculin-negative schoolchildren in the Czech Republic. The analysis is conducted from the perspective of the payer for health care. In considering whether revaccination should be discontinued, we consistently made assumptions which tend to favor revaccination. The direct costs of revaccination are estimated at Czech Koruna (KCR) 15.0 million (US$0.46 million) annually. The direct benefits are the treatment costs saved for future cases averted by revaccination. These range from KCR 0.5 million (US$0.015 million, ambulatory care, excluding transmission benefits) to KCR 13.7 million (US$0.4 million, hospitalization, including transmission benefits). Costs exceed benefits even if children are revaccinated without prior tuberculin testing. The major indirect cost is the loss of work output attributable to tuberculosis morbidity. Counting the averted loss in output as a benefit does not change the results qualitatively, although there is a 50% chance that the benefits will be greater than costs if treatment continues to be hospital-based. Thus, the costs of revaccination in the Czech Republic are found to exceed benefits over most, plausible variations in parameter values. The cost–benefit ratio is especially large if patients are given ambulatory treatment, as recommended by the World Health Organization.
The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection that experience clinically significant outcomes and to study factors related to these outcomes. Enrollment commenced in October 2009 and will continue until August 2011: as of the end of 2010, 62 sites in 14 countries in Australasia (12 sites), Europe (37) and North America (13) have enrolled 1365 adult patients, with 1049 enrollments into the FLU 002 outpatient study and 316 into the FLU 003 hospitalization study. These 'in progress' INSIGHT influenza observational studies may act as a model for obtaining epidemiological, clinical and laboratory information in future international disease outbreaks.
The differences in incidence rates of Haemophilus influenzae type b disease and the variation in Hib conjugate vaccine efficacy achieved among different ethnic groups suggest genetic influences on the immune response to Hib vaccine. The serum anti-PRP antibody concentration of 43 monozygotic (MZ) and 147 dizygotic (DZ) twin pairs in the Gambia was measured using a standardised Hib ELISA. Intrapair correlations for MZ and DZ twin pairs were compared and heritability in antibody responses to Hib conjugate vaccine was estimated to be 51% (95% CI: 32-66%), indicating a significant genetic contribution in the response. We conclude that genetic factors may be involved in the variation in immune response to Hib vaccine observed in different populations and may contribute to cases of vaccine failure.