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2.
Nat Commun ; 13(1): 1726, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1773977

ABSTRACT

Immunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity.


Subject(s)
Asymptomatic Infections , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel , Humans , Immunization , SARS-CoV-2 , Vaccination
3.
BMJ ; 376: o818, 2022 Mar 30.
Article in English | MEDLINE | ID: covidwho-1769884

Subject(s)
Immunization , Parents , Humans
4.
Immunology ; 164(1): 15-30, 2021 09.
Article in English | MEDLINE | ID: covidwho-1769724

ABSTRACT

ADP-ribosylation is the addition of one or more (up to some hundreds) ADP-ribose moieties to acceptor proteins. This evolutionary ancient post-translational modification (PTM) is involved in fundamental processes including DNA repair, inflammation, cell death, differentiation and proliferation, among others. ADP-ribosylation is catalysed by two major families of enzymes: the cholera toxin-like ADP-ribosyltransferases (ARTCs) and the diphtheria toxin-like ADP-ribosyltransferases (ARTDs, also known as PARPs). ARTCs sense and use extracellular NAD, which may represent a danger signal, whereas ARTDs are present in the cell nucleus and/or cytoplasm. ARTCs mono-ADP-ribosylate their substrates, whereas ARTDs, according to the specific family member, are able to mono- or poly-ADP-ribosylate target proteins or are devoid of enzymatic activity. Both mono- and poly-ADP-ribosylation are dynamic processes, as specific hydrolases are able to remove single or polymeric ADP moieties. This dynamic equilibrium between addition and degradation provides plasticity for fast adaptation, a feature being particularly relevant to immune cell functions. ADP-ribosylation regulates differentiation and functions of myeloid, T and B cells. It also regulates the expression of cytokines and chemokines, production of antibodies, isotype switch and the expression of several immune mediators. Alterations in these processes involve ADP-ribosylation in virtually any acute and chronic inflammatory/immune-mediated disease. Besides, pathogens developed mechanisms to contrast the action of ADP-ribosylating enzymes by using their own hydrolases and/or to exploit this PTM to sustain their virulence. In the present review, we summarize and discuss recent findings on the role of ADP-ribosylation in immunobiology, immune evasion/subversion by pathogens and immune-mediated diseases.


Subject(s)
ADP-Ribosylation/immunology , Alarmins/metabolism , Virus Diseases/immunology , Animals , Humans , Immune Evasion , Immunity, Cellular , Immunization , Inflammation , Virulence
6.
Pediatr Infect Dis J ; 41(5): e188-e193, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1764688

ABSTRACT

BACKGROUND: Recent global outbreaks of vaccine-preventable diseases, both before and since the coronavirus disease 2019 pandemic, have led to the introduction or strengthening of vaccine mandate policies to target vaccine refusal. Globally, there is wide variation in how governments and jurisdictions implement and enforce mandatory vaccination as well as the financial and educational consequences to those who fail to comply. We explored the impact of mandate vaccination policies on Australian Immunization Specialists who work in Specialist Immunization Clinics (SIC) for approving vaccine exemptions outside of the mandated criteria. In particular, their interactions with patients and families. METHODS: A national, prospective, mixed methods, survey-based study conducted with members of the Australian Adverse Event Following Immunisation Clinical Assessment Network between February 2020 and June 2020. RESULTS: Sixteen Immunization physicians and nurse practitioner specialists working in a SIC completed the survey. All sixteen respondents had been requested by parents to provide a Medical Exemptions at least once. 88% of respondents felt pressure to provide an exemption that was not medically justified according to legislation. Seventy-five percent of SIC consultants felt that the "No Jab" policies created a moderate or extreme amount of stress to both themselves and parents. All respondents reported experiencing hostility from parents with three respondents having received threats of violence. CONCLUSIONS: Mandatory vaccination policies are associated with increased vaccination coverage but can result in widened financial and social inequity, and may harm families' relationships with health care providers. Countries considering the implementation of vaccination mandates should use the least restrictive health policies to ensure a balance between the public health and individual benefit whilst minimizing burdens on health care professionals, children and their parents.


Subject(s)
COVID-19 , Vaccines , Australia/epidemiology , Child , Health Policy , Humans , Immunization , Immunization Programs , Parents , Prospective Studies , Vaccination , Vaccines/adverse effects
7.
Bull World Health Organ ; 100(2): 115-126C, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1760156

ABSTRACT

Objective: To examine changes in vaccination of children younger than 1 year during the coronavirus disease 2019 (COVID-19) pandemic (March 2020-August 2021) in Haiti, Lesotho, Liberia and Malawi. Methods: We used data from health management information systems on vaccination of children aged 12 months or younger in districts supported by Partners In Health. We used data from January 2016 to February 2020 and a linear model with negative binomial distribution to estimate the expected immunization counts for March 2020-August 2021 with 95% prediction intervals, assuming no pandemic. We compared these expected levels with observed values and estimated the immunization deficits or excesses during the pandemic months. Findings: Baseline vaccination counts varied substantially by country, with Lesotho having the lowest count and Haiti the highest. We observed declines in vaccination administration early in the COVID-19 pandemic in Haiti, Lesotho and Liberia. Continued declines largely corresponded to high rates of COVID-19 infection and discrete stock-outs. By August 2021, vaccination levels had returned to close to or above expected levels in Haiti, Liberia and Lesotho; in Malawi levels remained below expected. Conclusion: Patterns of childhood immunization coverage varied by country over the course of the pandemic, with significantly lower than expected vaccination levels seen in one country during subsequent COVID-19 waves. Governments and health-care stakeholders should monitor vaccine coverage closely and consider interventions, such as community outreach, to avoid or combat the disruptions in childhood vaccination.


Subject(s)
COVID-19 , Child , Haiti/epidemiology , Humans , Immunization , Immunization Programs , Infant , Lesotho/epidemiology , Liberia/epidemiology , Malawi/epidemiology , Pandemics , SARS-CoV-2 , Vaccination
8.
PLoS Pathog ; 18(2): e1010282, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753213

ABSTRACT

Immunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites (IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development. Trial registration: ClinicalTrials.gov NCT01994525.


Subject(s)
Immunity , Inflammation , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Sporozoites/immunology , Adult , Animals , Anopheles/parasitology , Female , Humans , Immunization/methods , Insect Bites and Stings/immunology , Malaria, Falciparum/parasitology , Male , Mosquito Vectors/parasitology , T-Lymphocytes/immunology , Vaccination/methods , Vaccines, Attenuated/immunology
9.
BMJ Open ; 12(3): e057245, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1745688

ABSTRACT

OBJECTIVE: Immunisations are highly impactful, cost-effective public health interventions. However, substantial gaps in complete vaccination coverage persist. We aimed to describe caregivers' immunisation experiences and identify determinants of vaccine dropout. DESIGN: We used a community-based participatory research approach employing Photovoice, SMS (short messaging service) exchanges and in-depth interviews. A team-based approach was used for thematic analysis. The Increasing Vaccination Model guided the analysis and identification of vaccination facilitators and barriers. SETTING: This study was conducted in Zambézia province, Mozambique, in Namarroi and Gilé districts, where roughly 19% of children under 2 start but do not complete the recommended vaccination schedule. PARTICIPANTS: Participants were identified through health facility vaccination records and included caregivers of children aged 25-34 months who were fully vaccinated (n=10) and partially vaccinated (n=22). We also collected data from 12 health workers responsible for delivering immunisations at the selected health facilities. RESULTS: Four main patterns of barriers leading to dropout emerged: (1) social norms and limited family support place the immunisation burden on mothers; (2) perceived poor quality of health services reduces caregivers' trust in vaccination services; (3) concern about side effects causes vaccine hesitancy; and (4) caregivers hesitate to seek and advocate for vaccination due to power imbalances with health workers. COVID-19 created additional barriers related to social distancing, mask requirements, supply chain challenges and disrupted outreach services. For most caregivers, dropout becomes increasingly likely with compounding barriers. Caregivers of fully-vaccinated children noted facilitators, including accompaniment to health facilities or assistance caring for other children, which enabled them to complete vaccination. CONCLUSIONS: Overcoming immunisation barriers requires strengthening health systems, including improving logistics to avert vaccine stockouts and building health worker capacity, including empathic communication with caregivers. Consistent and reliable immunisation outreach services could address access challenges and improve immunisation uptake, particularly in distant communities.


Subject(s)
COVID-19 , Community-Based Participatory Research , Child , Child, Preschool , Female , Humans , Immunization , Mozambique , Vaccination
10.
Front Immunol ; 13: 840707, 2022.
Article in English | MEDLINE | ID: covidwho-1742222

ABSTRACT

The development of effective vaccines against SARS-CoV-2 remains a global health priority. Despite extensive use, the effects of Sputnik V on B cell immunity need to be explored in detail. We performed comprehensive profiling of humoral and B cell responses in a cohort of vaccinated subjects (n = 22), and demonstrate that Sputnik vaccination results in robust B cell immunity. We show that B memory cell (MBC) and antibody responses to Sputnik V were heavily dependent on whether the vaccinee had a history of SARS-CoV-2 infection or not. 85 days after the first dose of the vaccine, ex vivo stimulated MBCs from the vast majority of Sputnik V vaccinees produced antibodies that robustly neutralized the Wuhan Spike-pseudotyped lentivirus. MBC-derived antibodies from all previously infected and some of the naïve vaccine recipients could also cross-neutralize Beta (B.1.351) variant of SARS-CoV-2. Virus-neutralizing activity of MBC-derived antibodies correlated well with that of the serum antibodies, suggesting the interplay between the MBC and long-lived plasma cell responses. Thus, our in-depth analysis of MBC responses in Sputnik V vaccinees complements traditional serological approaches and may provide important outlook into future B cell responses upon re-encounter with the emerging variants of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Vaccines, Synthetic/immunology , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Cells, Cultured , Cohort Studies , Female , Humans , Immunization , Male , Middle Aged , Vaccination
11.
Front Immunol ; 13: 827605, 2022.
Article in English | MEDLINE | ID: covidwho-1742217

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of international concern, and an effective vaccine is urgently needed to control the pandemic. Envelope (E) and membrane (M) proteins are highly conserved structural proteins among SARS-CoV-2 and SARS-CoV and have been proposed as potential targets for the development of cross-protective vaccines. Here, synthetic DNA vaccines encoding SARS-CoV-2 E/M proteins (called p-SARS-CoV-2-E/M) were developed, and mice were immunised with three doses via intramuscular injection and electroporation. Significant cellular immune responses were elicited, whereas no robust humoral immunity was detected. In addition, novel H-2d-restricted T-cell epitopes were identified. Notably, although no drop in lung tissue virus titre was detected in DNA-vaccinated mice post-challenge with SARS-CoV-2, immunisation with either p-SARS-CoV-2-E or p-SARS-CoV-2-M provided minor protection and co-immunisation with p-SARS-CoV-2-E+M increased protection. Therefore, E/M proteins should be considered as vaccine candidates as they may be valuable in the optimisation of vaccination strategies against COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Coronavirus Envelope Proteins/genetics , Coronavirus M Proteins/genetics , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Animals , Antibodies, Viral/blood , COVID-19 Vaccines/genetics , Female , Humans , Immunization , Mice , Mice, Inbred BALB C , Vaccines, DNA
12.
BMJ Open ; 12(3): e055815, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1741634

ABSTRACT

OBJECTIVE: In this study, we assess the indirect impact of COVID-19 on utilisation of immunisation and outpatient services in Kenya. DESIGN: Longitudinal study. SETTING: Data were analysed from all healthcare facilities reporting to Kenya's health information system from January 2018 to March 2021. Multiple imputation was used to address missing data, interrupted time series analysis was used to quantify the changes in utilisation of services and sensitivity analysis was carried out to assess robustness of estimates. EXPOSURE OF INTEREST: COVID-19 outbreak and associated interventions. OUTCOME MEASURES: Monthly attendance to health facilities. We assessed changes in immunisation and various outpatient services nationally. RESULTS: Before the first case of COVID-19 and pursuant intervention measures in March 2020, uptake of health services was consistent with historical levels. There was significant drops in attendance (level changes) in April 2020 for overall outpatient visits for under-fives (rate ratio, RR 0.50, 95% CI 0.44 to 0.57), under-fives with pneumonia (RR 0.43, 95% CI 0.38 to 0.47), overall over-five visits (RR 0.65, 95% CI 0.57 to 0.75), over-fives with pneumonia (RR 0.62, 95% CI 0.55 to 0.70), fourth antenatal care visit (RR 0.86, 95% CI 0.80 to 0.93), total hypertension (RR 0.89, 95% CI 0.82 to 0.96), diabetes cases (RR 0.95 95% CI, 0.93 to 0.97) and HIV testing (RR 0.97, 95% CI 0.94 to 0.99). Immunisation services, first antenatal care visits, new cases of hypertension and diabetes were not affected. The post-COVID-19 trend was increasing, with more recent data suggesting reversal of effects and health services reverting to expected levels as of March 2021. CONCLUSION: COVID-19 pandemic has had varied indirect effects on utilisation of health services in Kenya. There is need for proactive and targeted interventions to reverse these effects as part of the pandemic's response to avert non-COVID-19 indirect mortality.


Subject(s)
COVID-19 , Ambulatory Care , COVID-19/epidemiology , COVID-19/prevention & control , Female , Humans , Immunization , Interrupted Time Series Analysis , Kenya/epidemiology , Longitudinal Studies , Outpatients , Pandemics , Pregnancy , SARS-CoV-2
13.
Vaccine ; 40(13): 1977-1986, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1740256

ABSTRACT

In 2020, the World Health Organization launched the Immunization Agenda 2030: A Global Strategy to Leave No One Behind, which prioritizes high equitable immunization coverage at the national level and in all districts. Achieving high and homogenous immunization coverage, which is all the more important within the current context of the COVID-19 pandemic and vaccine rollout, requires the strengthening of existing immunization activities and innovative approach to immunization promotion. This research applied a descriptive case study methodology to document the implementation of strategic multi-level alliances to promote equitable immunization access and demand in Colombia, Guyana, and Sucre, Bolivia. Data collection, carried out between September 2019 and March 2020, included documentary reviews, semi-structured interviews, focus groups, and site visits accompanied by discussions with relevant stakeholders. Case studies provide valuable examples of people-centered, partnership-based, country-owned, and data-guided approaches to promoting equitable immunization coverage, including multi-level partnerships to build technical capacity for the identification and measurement of social inequalities impacting immunization in Colombia; intersectoral and community collaboration for pro-equity emergency response to regional vaccine preventable disease outbreaks in Guyana; and strategic alliances with the education sector and civil society organizations for the introduction of the human papilloma virus (HPV) vaccine in Sucre, Bolivia. Lessons learned highlight avenues for improving the impact of multi-level, equity-focused capacity building, particularly at the local level; optimizing the use of data and resources, partnerships, and community and stakeholder education and empowerment. While impact studies are needed to better understand the quantitative contributions of such strategic alliances, these case studies illustrate their practical significance and reinforce the value of multi-level, intersectoral collaboration for enhancing equitable immunization access and demand. The experiences of Colombia, Guyana, and Sucre, Bolivia provide evidence-based insight to support pro-equity immunization program planning to ensure that no one is left behind and that everyone, everywhere receives the benefits of vaccines, both routine and for COVID-19.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , Caribbean Region , Humans , Immunization , Immunization Programs , Latin America , Pandemics/prevention & control
14.
In Vivo ; 36(2): 954-960, 2022.
Article in English | MEDLINE | ID: covidwho-1732570

ABSTRACT

BACKGROUND/AIM: Multiple reports from all over the world link COVID-19 with endothelial/coagulation disorders as well as a dysregulated immune response. This study tested the hypothesis that immunostimulation will be greater in COVID-19 patients than in patients with H1N1 infection or bacterial sepsis. Also, whether an increase in immune stimulation will be accompanied by a more severely affected endothelium/coagulation system was examined. PATIENTS AND METHODS: Twenty-three septic patients, admitted in the Intensive Care Unit (ICU), were enrolled (9 with SARS-CoV-2, 5 with H1N1 pneumonia, 9 with bacterial sepsis). Myeloperoxidase (MPO) activity along with certain endothelial/coagulation factors were assessed on admission (time point 1) and at either improvement or deterioration (time point 2). RESULTS: MPO levels were significantly higher in COVID-19 patients compared to both other groups. Furthermore, in patients with COVID-19, vWF levels did not differ significantly, fVIII levels were lower while ADAMTS-13 activity was higher compared to patients with H1N1 pneumonia and bacterial sepsis (a trend in the latter). CONCLUSION: Increased immunostimulation was noted in COVID-19 patients compared to other septic patients; however, this was not accompanied by greater disturbance of the clotting system and/or more severe endothelial injury.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Influenza A Virus, H1N1 Subtype , Sepsis , Blood Coagulation Disorders/etiology , COVID-19/complications , Humans , Immunization , SARS-CoV-2 , Sepsis/complications
15.
Front Immunol ; 13: 798813, 2022.
Article in English | MEDLINE | ID: covidwho-1725390

ABSTRACT

A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals. Methods: A longitudinal cohort of healthcare workers (HCW, N = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response. Results: We identified three risk groups to develop SARS-CoV-2 infection IgG+-based (late responders, R-; early responders, R+; pauci responders, PR). In all receipts, amplification of B cells and NK cells, including IL4-producing B cells and IL4-producing CD8+ T cells, is early stimulated by the vaccine. After the boost, we observed a growing increase of NK cells but a resistance of T cells, IFNγ-producing CD4+T cells, and IFNγ-producing NK cells. Also, hematologic parameters decline until the boost. The positive association of IFNγ-producing NK with IFNγ-producing CD4+T cells by the multiple mixed-effect model, adjusted for confounders (p = 0.036) as well as the correlation matrix (r = 0.6, p < 0.01), suggests a relationship between these two subsets of lymphocytes. Conclusions: These findings introduce several concerns about policy delay in vaccination: based on immunological protection, B cells and the persistent increase of NK cells during 2 doses of the mRNA-based vaccine could provide further immune protection against the virus, while CD8+ T cells increased slightly only in the R+ and PR groups.


Subject(s)
/immunology , Immunization , Interferon-gamma/immunology , Killer Cells, Natural/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , Female , Humans , Interleukin-4/immunology , Leukocytes, Mononuclear/immunology , Lymphocyte Subsets/immunology , Male , Th1-Th2 Balance
16.
PLoS Med ; 19(2): e1003934, 2022 02.
Article in English | MEDLINE | ID: covidwho-1708110

ABSTRACT

Kate Causey and Jonathan F Mosser discuss what can be learnt from the observed impacts of the COVID-19 pandemic on routine immunisation systems.


Subject(s)
COVID-19/prevention & control , Immunization , SARS-CoV-2/pathogenicity , Vaccination/statistics & numerical data , Humans , Immunization Programs/methods
18.
Front Public Health ; 9: 801176, 2021.
Article in English | MEDLINE | ID: covidwho-1701305

ABSTRACT

Rather than concentrating primarily on children and adolescents, there has been a shift in the discourse around immunisation to encompass a whole-of-life approach. Despite this acknowledgement and ongoing high burdens of vaccine preventable diseases in adults, coverage for some adult risk groups remains sub-optimal. This study aimed to explore key informant's and stakeholder's perceptions of factors impacting provision of immunisation programs for Australian adults and to identify strategies to promote acceptance and uptake. Semi-structured telephone interviews were undertaken with people involved in adult immunisation program delivery, advocacy, policy or research between September 2020 and June 2021. Transcripts were inductively analysed, with the resulting themes categorised into the five influences on vaccination gaps that have informed program planning in other countries: Access, Affordability, Awareness, Acceptance and Activation. Participants spoke of improvements in the provision of vaccines to adults, however, ongoing challenges persisted. Participants agreed that the focus or emphasis of policies and the promotion/communication strategies has been on childhood vaccination in Australia, however there is a sense that the "pendulum has swung." These included understanding of eligibility amongst the Australian population and the reluctance of some health providers to dedicate time to exploring immunisation needs with adult patients. In comparison to the childhood vaccination program, there has been a lack of data available on coverage for adult vaccines on the national immunisation program. This has contributed to the ongoing challenges of identifying and promoting certain vaccines. At a government level, questions were raised about why the Australian government has never set an aspirational target for adult vaccination (i.e., influenza or pneumococcal) coverage. While significant improvements have been made in adult immunisation uptake, there are still gaps across the program. While the system remains under stress because of the COVID-19 pandemic, it is not appropriate to implement any additional programs. There needs to be strong commitment to establish the value of adult vaccination in the eyes of community members, policy makers and healthcare professionals. Having a national adult immunisation strategic plan would help advance action.


Subject(s)
COVID-19 , Influenza Vaccines , Adolescent , Adult , Australia/epidemiology , Child , Humans , Immunization , Life Change Events , Pandemics , SARS-CoV-2 , Vaccination
20.
Cell ; 185(4): 614-629.e21, 2022 02 17.
Article in English | MEDLINE | ID: covidwho-1676664

ABSTRACT

Activation of the innate immune system via pattern recognition receptors (PRRs) is key to generate lasting adaptive immunity. PRRs detect unique chemical patterns associated with invading microorganisms, but whether and how the physical properties of PRR ligands influence the development of the immune response remains unknown. Through the study of fungal mannans, we show that the physical form of PRR ligands dictates the immune response. Soluble mannans are immunosilent in the periphery but elicit a potent pro-inflammatory response in the draining lymph node (dLN). By modulating the physical form of mannans, we developed a formulation that targets both the periphery and the dLN. When combined with viral glycoprotein antigens, this mannan formulation broadens epitope recognition, elicits potent antigen-specific neutralizing antibodies, and confers protection against viral infections of the lung. Thus, the physical properties of microbial ligands determine the outcome of the immune response and can be harnessed for vaccine development.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antigens, Viral/immunology , Candida albicans/chemistry , Mannans/immunology , Aluminum Hydroxide/chemistry , Animals , Antibodies, Neutralizing/immunology , Antibody Specificity/immunology , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Epitopes/immunology , Immunity, Innate , Immunization , Inflammation/pathology , Interferons/metabolism , Lectins, C-Type/metabolism , Ligands , Lung/immunology , Lung/pathology , Lung/virology , Lymph Nodes/immunology , Lymph Nodes/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , Paranasal Sinuses/metabolism , Protein Subunits/metabolism , Sialic Acid Binding Ig-like Lectin 1/metabolism , Solubility , Spike Glycoprotein, Coronavirus/metabolism , T-Lymphocytes/immunology , Transcription Factor RelB/metabolism , Vero Cells , beta-Glucans/metabolism
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