Evaluation of Pneumonia Virus of Mice as a Possible Human Pathogen

Pneumonia virus of mice (PVM), a relative of human respiratory syncytial virus (RSV), causes respiratory disease in mice. There is serologic evidence suggesting widespread exposure of humans to PVM. To investigate replication in primates, African green monkeys (AGM) and rhesus macaques (n=4) were inoculated with PVM by the respiratory route. Virus was shed intermittently at low levels by a subset of animals, suggesting poor permissiveness. PVM efficiently replicated in cultured human cells and inhibited the type I interferon (IFN) response in these cells. This suggests that poor replication in nonhuman primates was not due to a general nonpermissiveness of primate cells or poor control of the IFN response. Seroprevalence in humans was examined by screening sera from 30 adults and 17 young children for PVM-neutralizing activity. Sera from a single child (6%) and 40% of adults had low neutralizing activity against PVM, which could be consistent with increasing incidence of exposure following early childhood. There was no cross-reaction of human or AGM sera between RSV and PVM and no cross-protection in the mouse model. In native Western blots, human sera reacted with RSV but not PVM proteins under conditions in which AGM immune sera reacted strongly. Serum reactivity was further evaluated by flow cytometry using unfixed Vero cells infected with PVM or RSV expressing green fluorescent protein (GFP) as a measure of viral gene expression. The reactivity of human sera against RSV-infected cells correlated with GFP expression, whereas reactivity against PVM-infected cells was low and uncorrelated with GFP expression. Thus, PVM specificity was not evident. Our results indicate that the PVM-neutralizing activity of human sera is not due to RSV- or PVM-specific antibodies but may be due to low-affinity, polyreactive natural antibodies of the IgG subclass. The absence of PVM-specific antibodies and restriction in nonhuman primates makes PVM unlikely to be a human pathogen

Specimen collection for the diagnosis of pediatric pneumonia.

Diagnosing the etiologic agent of pneumonia has an essential role in ensuring the most appropriate and effective therapy for individual patients and is critical to guiding the development of treatment and prevention strategies. However, establishing the etiology of pneumonia remains challenging because of the relative inaccessibility of the infected tissue and the difficulty in obtaining samples without contamination by upper respiratory tract secretions. Here, we review the published and unpublished literature on various specimens available for the diagnosis of pediatric pneumonia. We discuss the advantages and limitations of each specimen, and discuss the rationale for the specimens to be collected for the Pneumonia Etiology Research for Child Health study

Clinical trials and pregnancy

Traditionally, there has been a reluctance to involve pregnant people in clinical trials due to complex ethical issues surrounding the risk to unborn babies. However it is crucial that new interventions are safe and effective for all patients and ensuring this can be difficult to achieve in the absence of clinical trials

Conspiracy theories and misinformation about COVID-19 in Nigeria: Implications for vaccine demand generation communications.

INTRODUCTION: COVID-19 vaccine hesitancy is a worldwide phenomenon and a serious threat to pandemic control efforts. Until recently, COVID-19 vaccine hesitancy was not the cause of low vaccine coverage in Nigeria; vaccine scarcity was the problem. As the global supply of COVID-19 vaccines improves in the second half of 2021 and more doses are deployed in Nigeria, the supply/demand dynamic will switch. Vaccine acceptance will become a key driver of coverage; thus, amplifying the impact of vaccine hesitancy. Conspiracy theories and misinformation about COVID-19 are rampant and have been shown to drive vaccine hesitancy and refusal. This study systematically elicits the misinformation and conspiracy theories circulating about COVID-19 among the Nigerian public to understand relevant themes and potential message framing for communication efforts to improve vaccine uptake. METHODS: From February 1 to 8, 2021, we conducted 22 focus group discussions and 24 key informant interviews with 178 participants from six states representing the six geopolitical zones. Participants were purposively selected and included sub-national program managers, healthcare workers, and community members. All interviews were iteratively analyzed using a framework analysis approach. RESULTS: We elicited a total of 33 different conspiracy theories or misinformation that participants had heard about the COVID-19 virus, pandemic response, or vaccine. All participants had heard some misinformation. The leading claim was that COVID-19 was not real, and politicians took advantage of the situation and misused funds. People believed certain claims based on distrust of government, their understanding of Christian scripture, or their lack of personal experience with COVID-19. CONCLUSIONS: Our study is the first to report a thematic analysis of the range of circulating misinformation about COVID-19 in Nigeria. Our findings provide new insights into why people believe these theories, which could help the immunization program improve demand generation communication for COVID-19 vaccines by targeting unsubstantiated claims

Data and product needs for influenza immunization programs in low- and middle-income countries: Rationale and main conclusions of the WHO preferred product characteristics for next-generation influenza vaccines.

In 2017, WHO convened a working group of global experts to develop the Preferred Product Characteristics (PPC) for Next-Generation Influenza Vaccines. PPCs are intended to encourage innovation in vaccine development. They describe WHO preferences for parameters of vaccines, in particular their indications, target groups, implementation strategies, and clinical data needed for assessment of safety and efficacy. PPCs are shaped by the global unmet public health need in a priority disease area for which WHO encourages vaccine development. These preferences reflect WHO's mandate to promote the development of vaccines with high public health impact and suitability in Low- and Middle-Income Countries (LMIC). The target audience is all entities intending to develop or to achieve widespread adoption of a specific influenza vaccine product in these settings. The working group determined that existing influenza vaccines are not well suited for LMIC use. While many developed country manufactures and research funders prioritize influenza vaccine products for use in adults and the elderly, most LMICs do not have sufficiently strong health systems to deliver vaccines to these groups. Policy makers from LMICs are expected to place higher value on vaccines indicated for prevention of severe illness, however the clinical development of influenza vaccines focuses on demonstrating prevention of any influenza illness. Many influenza vaccine products do not meet WHO standards for programmatic suitability of vaccines, which introduces challenges when vaccines are used in low-resource settings. And finally, current vaccines do not integrate well with routine immunization programs in LMICs, given age of vaccine licensure, arbitrary expiration dates timed for temperate country markets, and the need for year-round immunization in countries with prolonged influenza seasonality. While all interested parties should refer to the full PPC document for details, in this article we highlight data needs for new influenza vaccines to better demonstrate the value proposition in LMICs

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.Fil: Krubiner, Carleigh B.. University Johns Hopkins; Estados UnidosFil: Faden, Ruth R.. University Johns Hopkins; Estados UnidosFil: Karron, Ruth A.. University Johns Hopkins; Estados UnidosFil: Little, Margaret O.. University Of Georgetown; Estados UnidosFil: Lyerly, Anne D.. University of North Carolina; Estados UnidosFil: Abramson, Jon S.. University Wake Forest; Estados UnidosFil: Beigi, Richard H.. Magee-Womens Hospital of University of Pittsburgh Medical Center; Estados UnidosFil: Cravioto, Alejandro R.. Universidad Nacional Autónoma de México; MéxicoFil: Durbin, Anna P.. University Johns Hopkins; Estados UnidosFil: Gellin, Bruce G.. Sabin Vaccine Institute; Estados UnidosFil: Gupta, Swati B.. IAVI; Estados UnidosFil: Kaslow, David C.. PATH; Estados UnidosFil: Kochhar, Sonali. Global Healthcare Consulting; IndiaFil: Luna, Florencia. Facultad Latinoamericana de Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saenz, Carla. Pan American Health Organization; Estados UnidosFil: Sheffield, Jeanne S.. University Johns Hopkins; Estados UnidosFil: Tindana, Paulina O.. Navrongo Health Research Centre; GhanaFil: The Prevent Working Group. No especifíca

A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incident precluded development of subunit RSV vaccines for infants for over 30 years, because the mechanism of illness was never clarified. An RSV vaccine for infants is still not available

Respiratory syncytial virus vaccine research and development: World Health Organization technological roadmap and preferred product characteristics.

The respiratory syncytial virus causes a considerable respiratory disease burden globally, most markedly in young infants, in low and middle income countries. A diverse product pipeline illustrates the recent intensification of research and development activities for vaccines and monoclonal antibodies against RSV. With the aim to ensure that product development activities are directed to address the public health needs, the World Health Organization has developed a research and development technical roadmap and articulated product characteristics preferences