Measuring Vaccine Responses in the Multiplex Era

Author(s):  
Kieran Ayling ◽  
Kavita Vedhara ◽  
Lucy Fairclough
Keyword(s):  
BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1457
Author(s):  
Dewald Schoeman ◽  
Burtram C. Fielding

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.


Author(s):  
Jack Arnold ◽  
Kevin Winthrop ◽  
Paul Emery

Abstract The coronavirus disease 2019 (COVID-19) vaccination will be the largest vaccination programme in the history of the NHS. Patients on immunosuppressive therapy will be among the earliest to be vaccinated. Some evidence indicates immunosuppressive therapy inhibits humoral response to the influenza, pneumococcal and hepatitis B vaccines. The degree to which this will translate to impaired COVID-19 vaccine responses is unclear. Other evidence suggests withholding MTX for 2 weeks post-vaccination may improve responses. Rituximab has been shown to impair humoral responses for 6 months or longer post-administration. Decisions on withholding or interrupting immunosuppressive therapy around COVID-19 vaccination will need to be made prior to the availability of data on specific COVID-19 vaccine response in these patients. With this in mind, this article outlines the existing data on the effect of antirheumatic therapy on vaccine responses in patients with inflammatory arthritis and formulates a possible pragmatic management strategy for COVID-19 vaccination.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jun Deng ◽  
Qian Chen ◽  
Zhian Chen ◽  
Kaili Liang ◽  
Xin Gao ◽  
...  

AbstractFollicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.


Author(s):  
Chloe Rees-Spear ◽  
Laura E McCoy

Abstract Lay Summary Improved life expectancy in recent years has led to a growing population of adults over the age of 60. Age is commonly associated with increased inflammatory conditions and infections. Similar immunological changes have been observed during chronic infections, in particular HIV, where this is compounded by the success of antiretroviral therapy that has increased the number of people living with HIV into their sixties and beyond. The increased susceptibility of these groups to infection makes vaccination all the more important. However, the alterations to their immune systems call into question how effective those vaccinations may be. Here we discuss vaccine efficacy within elderly and chronically infected populations and investigate the immunological changes that may impact vaccine responsiveness. Over the last few decades, changing population demographics have shown that there is a growing number of individuals living past the age of 60. With this expanding older population comes an increase in individuals that are more susceptible to chronic illness and disease. An important part of maintaining health in this population is through prophylactic vaccination, however, there is growing evidence that vaccines may be less effective in the elderly. Furthermore, with the success of anti-viral therapies, chronic infections such as HIV are becoming increasingly prevalent in older populations and present a relatively unstudied population with respect to the efficacy of vaccination. Here we will examine the evidence for age-associated reduction in antibody and cellular responsiveness to a variety of common vaccines, and investigate the underlying causes attributed to this phenomenon, such as inflammation and senescence. We will also discuss the impact of chronic viral infections on immune responses in both young and elderly patients, particularly those living with HIV, and how this affects vaccinations in these populations.


Author(s):  
Andrew Cox ◽  
Hilal Cevik ◽  
H. Alex Feldman ◽  
Laura M. Canaday ◽  
Nora Lakes ◽  
...  

Vaccine ◽  
2021 ◽  
Author(s):  
Michelle Clarke ◽  
Louise M. Goodchild ◽  
Sue Evans ◽  
Lynne C. Giles ◽  
Sheena G. Sullivan ◽  
...  

2020 ◽  
Vol 41 (S1) ◽  
pp. s185-s185
Author(s):  
Annie St-Pierre ◽  
Anne-Marie Charron ◽  
Pamela Doyon-Plourde ◽  
Caroline Quach

Background: In 2019, a measles community outbreak resulted in a secondary case in a health care worker (HCW) working in a pediatric hospital in Montral, Canada. Following the event, HCWs were screened to identify individuals susceptible to measles infection based on serology results. Objective: Our aim was to assess measles seroprotection rates and to evaluate vaccine responses of susceptible HCWs using commercial enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA). Methods: Emergency department (ED) employees, including doctors, were screened for measles susceptibility as part of a postoutbreak measure by the hospital occupational health service. Demographic information was collected. Measles history and vaccination information were collected using a personal vaccination booklet, employee vaccination profile, or the Qubec vaccination registry. According to the Quebec Immunization Protocol (PIQ), individuals born before 1970, or who have received 2 doses of a measles-containing vaccines are considered protected. Individuals with undetectable or equivocal antibody levels were considered at risk of measles infection. These individuals were offered vaccination and were tested for vaccine response 4 weeks after vaccination. Results: Anti-IgG measles antibody results, demographic information, and vaccination information were obtained for 257 employees. The results are currently available for 233 HCWs: 224 HCWs (96%) were seropositive, 7 (3%) were seronegative, and 2 were equivocal. Among seronegative individuals, 6 (85.7%) were born after 1980 and 3 (42.9%) had received 2 doses of a measles-containing vaccine. Of those with an equivocal result, 1 (50%) had received 2 doses and 1 (50%), born after 1970, did not confirm vaccination status. Finally, 9 (4%) of seropositive individuals were not vaccinated; of whom 8 (88.9%) were born before 1970. Conclusions: Our preliminary results suggest that the 95% immunity threshold that is usually required to prevent secondary transmission of measles has been reached in our ED HCW cohort. Even years after the second MMR dose, HCWs remain well protected. Relying on documented vaccination status is thus acceptable.Funding: NoneDisclosures: None


2000 ◽  
Vol 160 (13) ◽  
pp. 2017 ◽  
Author(s):  
Paul J. Carson ◽  
Kristin L. Nichol ◽  
James O'Brien ◽  
Pierre Hilo ◽  
Edward N. Janoff

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