Efficacy and immunogenicity of Mycobacterium bovis ΔRD1 against aerosol M. bovis infection in neonatal calves

An attenuated Mycobacterium bovisRD1 deletion (ΔRD1) mutant of the Ravenel strain was constructed, characterized, and sequenced. This M. bovis ΔRD1 vaccine strain administered to calves at 2 weeks of age provided similar efficacy as M. bovis bacillus Calmette Guerin (BCG) against low dose, aerosol challenge with virulent M. bovis at 3.5 months of age. Approximately 4.5 months after challenge, both ΔRD1- and BCG-vaccinates had reduced tuberculosis (TB)-associated pathology in lungs and lung-associated lymph nodes and M. bovis colonization of tracheobronchial lymph nodes as compared to non-vaccinates. Mean central memory responses elicited by either ΔRD1 or BCG prior to challenge correlated with reduced pathology and bacterial colonization. Neither ΔRD1 or BCG elicited IFN-γ responses to rESAT-6:CFP-10 prior to challenge, an emerging tool for modern TB surveillance programs. The ΔRD1 strain may prove useful for bovine TB vaccine programs, particularly if additional mutations are included to improve safety and immunogenicity.     

Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA–PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice

During persistent infection and hypoxic-stress, Mycobacterium tuberculosis (Mtb) expresses a series of Mtb latency antigens. The aim of this study was to evaluate the immunogenicity of a DNA vaccine encoding the Mtb latency antigen Rv1733c and to explore the effect of pulmonary delivery and co-formulation with poly (d,l-lactide-co-glycolide) (PLGA)–polyethyleneimine (PEI) nanoparticles (np) on host immunity. Characterization studies indicated that PLGA–PEI np kept their nanometer size after concentration and were positively charged. The np were able to mature human dendritic cells and stimulated them to secrete IL-12 and TNF-α comparable to levels observed after lipopolysaccharide (LPS) stimulation. Mtb latency antigen Rv1733c DNA prime combined with Rv1733c protein boost enhanced T cell proliferation and IFN-γ secretion in mice in response to Rv1733c and Mtb hypoxic lysate. Rv1733c DNA adsorbed to PLGA–PEI np and applied to the lungs increased T cell proliferation and IFN-γ production more potently compared to the same vaccinations given intramuscularly. The strongest immunogenicity was obtained by pulmonary priming with np-adsorbed Rv1733c DNA followed by boosting with Rv1733c protein. These results confirm that PLGA–PEI np are an efficient DNA vaccine delivery system to enhance T cell responses through pulmonary delivery in a DNA prime/protein boost vaccine regimen.     

Positive attitudes of French general practitioners towards A/H1N1 influenza-pandemic vaccination: A missed opportunity to increase vaccination uptakes in the general public?

Attitudes of general practitioners (GPs) towards A/H1N1 pandemic vaccination are unknown. We conducted a cross-sectional survey with computer-assisted telephone interviewing in the French Regional Panel of General Practices from June 16 to September 22, 2009. Of 1434 respondents representative of GPs in four French regions, 885 (61.7%) were willing to accept A/H1N1 pandemic vaccination for themselves. The personal history of seasonal flu vaccination was the strongest independent predictive factor of willingness to accept A/H1N1 pandemic vaccination (p < .0001). GPs receiving seasonal vaccines every year were more likely to accept A/H1N1 pandemic vaccination than those who were never vaccinated in the prior 3 years (adjusted OR = 4.38; 95% CI, 2.44–4.67). Willingness to accept pandemic vaccination was also significantly associated with being on call for emergencies; positive attitudes towards other protective measures against A/H1N1 influenza virus in the practice; and a higher readiness to provide additional consultations in response to the pandemic. In conclusion, GPs showed a high acceptability of A/H1N1 pandemic vaccination. GPs’ involvement in the mass vaccination campaign, which has been neglected by French public health authorities, may have increased uptake rates in the general public.     

The effect of Bacillus Calmette–Guérin (BCG) vaccination in preventing severe infectious respiratory diseases other than TB: Implications for the COVID-19 pandemic

The rapid spread of the Coronavirus pandemic and its significant health and social impact urges the search for effective and readily available solutions to mitigate the damages. Thus, evaluating the effectiveness of existing vaccines like Bacillus Calmette–Guérin (BCG) has attracted attention. The aim of this review was evidence synthesis on the effect of BCG vaccine in preventing severe infectious respiratory disease including COVD-19, but not tuberculosis. We considered studies conducted on human participants of any study design from any country setting that were published in Enlgish. We did a systematic literature search in MEDLINE, Scopus and Google scholar databases and a free search on Google. The identified studies were appraised and relevant data were extracted using Joanna Briggs Institute tools. The extracted findings were synthesized with tables and narrative summary. Nine studies met the inclusion criteria. The findings indicated that BCG vaccine has a strong protective effect against both upper and lower acute respiratory tract infections. For instance in countries with universal BCG vaccination policy, the incidence of COVID-19 was lower compared to the counterparts. Addtionally, BCG vaccine was found to protect against infections like lethal influenza A virus, pandemic influenza (H1N1), and other acute respiratory tract infections. BCG improved the human body’s immune response involving antigen-specific T cells and memory cells. It also induced adaptive functional reprogramming of mononuclear phagocytes that induce protective effects against different respiratory infections other than tuberculosis. In countries with universal BCG vaccination, the incidence and death from acute respiratory viral infection including COVID – 19 is significantly low. However, there is an urgent need for further evidence from well-designed studies to understand the possible role of BCG vaccination over time and across age groups, its possible benefits in special populations such as health workers and cost-savings related to a policy of universal BCG vaccination.     

The effect of immunization with inactivated SARS-CoV-2 vaccine (CoronaVac) and/or SARS-CoV-2 infection on antibody levels,plasmablasts, long-lived-plasma-cells,and IFN-γ release by natural killer cells

ObjectivesWe evaluated the antibody response, natural killer cell response and B cell phenotypes in healthcare workers (HCW) who are vaccinated with two doses of CoronaVac with or without documented SARS-CoV-2 infection and unvaccinated HCWs with SARS-CoV-2 infection.MethodsHCWs were divided into four groups: vaccine only (VO), vaccine after SARS-CoV-2 infection (VAI), SARS-CoV-2 infection only (IO), and SARS-CoV-2 infection after vaccine (IAV). Anti-SARS-CoV-2 spike protein (Anti-S) antibodies were measured by Elecsys Anti–SARS–CoV–2 S ELISA kit. Memory B cells (CD19⁺CD27⁺), plasmablast B cells (CD19⁺CD138⁺) and long-lived plasma cells (LLPC; CD138⁺CD19^-) were measured by flow cytometry in 74 patients. Interferon gamma (IFN-γ) release by natural killer (NK) cells were measured by NKVue Test (NKMAX, Republic of Korea) in 76 patients. RT-PCR was performed with Bio-speedy® COVID-19 qPCR detection kit, Version 2 (Bioexen LTD, Istanbul, Turkey).ResultsThe Anti-S antibodies were detectable in all HCWs (n: 224). The median Anti-S titers (BAU/mL) was significantly higher in VAI (620 25–75% 373–1341) compared to VO (136, 25–75% 85–283) and IO (111, 25–75% 54–413, p < 0.01). VAI group had significantly lower percentage of plasmablasts (2.9; 0–8.7) compared to VO (6.8; 3.5–12.0) and IO (9.9; 4.7–47.5, p < 0.01) (n:74). Percentage of LLPCs in groups VO, VAI and IO was similar. There was no difference of IFN-γ levels between the study groups (n: 76).ConclusionThe antibody response was similar between uninfected vaccinated HCWs and unvaccinated HCWs who had natural infection. HCWs who had two doses of CoronaVac either before or after the natural SARS-CoV-2 infection elicited significantly higher antibody responses compared to uninfected vaccinated HCWs. The lower percentages of plasmablasts in the VAI group may indicate their migration to lymph nodes and initiation of the germinal center reaction phase. IFN-γ response did not differ among the groups.     

Correlates of general practitioners’ recommendations to patients regarding vaccination for the 2009–2010 pandemic influenza (A/H1N1) in France: Implications for future vaccination campaigns

Background

General practitioners’ (GPs) recommendations to their patients regarding influenza vaccination is a key determinant of patient uptake of influenza vaccination.

Objectives

To study factors associated with GPs’ recommendations regarding pandemic vaccination (pvaccination) to adults ≤65 years of age (hereafter referred to as adults) at risk and not at risk of severe complications of the 2009–2010 A/H1N1 influenza.

Patients/Methods

National cross-sectional survey of 1431 French GPs. Pvaccination recommendations by GPs to adults were studied according to three categories: recommended pvaccination to at-risk adults only; recommended pvaccination to all adults; recommended against pvaccination or did not provide any advice to any adult.

Results

GPs were more likely to recommend pvaccination to at-risk than not-at-risk adults (73.4% vs 40.1%, p < 0.01). GPs who consulted official sources of information rather than news media during the pandemic were more likely to recommend pvaccination to at-risk adults only (OR = 1.78; CI 95% = 1.27–2.48) and to all adults (OR = 2.03; CI 95% = 1.42–2.92) than other GPs. GPs’ unfavorable perceptions of the risk/efficacy balance of the pandemic vaccine (pvaccine) together with their perceptions of the low severity of the disease were negatively associated with recommending pvaccination. Hospitalization of GPs’ patients because of the influenza was specifically associated with pvaccine recommendation to all adults (OR = 2.81; CI 95% = 1.98–3.99) but not with pvaccine recommendation to at-risk adults only.

Conclusion

In the pandemic context, GPs’ perceptions of disease severity and the risk/efficacy balance of the pvaccine were the major determinants of French GPs recommending pvaccination or not. To increase the general public's acceptability of vaccination policies, GPs should be adequately informed about the course of the epidemics and the safety of the vaccine.