Current approaches to the development of vaccines against disease caused by respiratory syncytial virus (RSV) and parainfluenza virus (PIV) A meeting report of the WHO Programme for Vaccine Development (original) (raw)
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Virus Research, 1994
RSV and PIV3 are responsible for about 30% of severe viral respiratory tract disease leading to hospitilization of infants and children. For this reason, there is a need to develop vaccines effective against these viruses. Since these viruses cause severe disease in early infancy, vaccines must be effective in the presence of maternal antibody. Currently, several strategies for immunization against these viruses are being explored including peptide vaccines, subunit vaccines, vectored vaccines (e.g., vaccinia-RSV or adenovirus-RSV recombinants), and live attenuated virus vaccines. The current status of these approaches is reviewed. In addition, the immunologic basis for the disease potentiation seen in vaccinees immunized with formalin-inactivated RSV during subsequent RSV infection is reviewed. The efficacy of immunization in the presence of maternal antibody is discussed. Much progress for a RSV and PIV3 vaccine has been made and successful immunization against each of these pathogens should be achieved within this decade.
New insights for development of a safe and protective RSV vaccine
Human Vaccines, 2010
Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and children <1 year old, resulting in significant morbidity and mortality worldwide. There is currently no RSV vaccine. In the 1960's, a formalin-inactivated RSV (FI-RSV) vaccine trial led to exacerbated disease upon natural infection of vaccinees, including two deaths. The causes involved in the disastrous results of these vaccine trials are still unclear but they remain the engine for searching new avenues to develop a safe vaccine that can provide long-term protection against this important pathogen. This article reviews some of the early history of RSV vaccine development, as well as more recent information on the interaction between RSV and the host innate and adaptive immune responses. A safe and efficacious vaccine for RSV will require "re-education" of the host immune response against RSV to prevent vaccine-enhanced or severe RSV disease.
A multifaceted approach to RSV vaccination
Human vaccines & immunotherapeutics, 2018
Respiratory Syncytial Virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. In addition, RSV infections occur throughout different ages, thus, maintaining the virus in circulation, and increasing health risk to more susceptible populations such as infants, the elderly, and the immunocompromised. To date, there is no vaccine approved to prevent RSV infection or minimize symptoms of infection. Current clinical trials for vaccines against RSV are being carried out in four very different populations. There are vaccines that target two different pediatric populations, infants 2 to 6 month of age and seropositive children over 6 months of age, as well as women (non-pregnant or pregnant in their third trimester). There are vaccines that target adult and elderly populations. In this review, we will present and discuss RSV vaccine candidates currently in clinical trials. We will describe the preclinical studies...
A respiratory syncytial virus (RSV) vaccine based on parainfluenza virus 5 (PIV5)
Vaccine, 2014
Human respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. It also causes significant morbidity and mortality in elderly and immune compromised individuals. No licensed vaccine currently exists. Parainfluenza virus 5 (PIV5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. To evaluate the efficacy of PIV5 as a RSV vaccine vector, we generated two recombinant PIV5 viruses -one expressing the fusion (F) protein and the other expressing the attachment glycoprotein (G) of RSV strain A2 (RSV A2). The vaccine strains were used separately for single-dose vaccinations in BALB/c mice. The results showed that both vaccines induced RSV antigen-specific antibody responses, with IgG2a/IgG1 ratios similar to those seen in wild-type RSV A2 infection. After challenging the vaccinated mice with RSV A2, histopathology of lung sections showed that the vaccines did not exacerbate lung lesions relative to RSV A2-immunized mice. Importantly, both F and G vaccines induced protective immunity. Therefore, PIV5 presents an attractive platform for vector-based vaccines against RSV infection.
Journal of Virology, 2020
Immune responses to RSV in infants can be reduced due to immunological immaturity and immunosuppression by RSV-specific maternal antibodies. In infants and young children, two infections with wild-type RSV typically are needed to achieve the titers of RSV-specific serum antibodies and protection against illness that are observed in adults. Therefore, a boost might substantially improve the performance of live pediatric RSV vaccines presently being developed. Hamsters and African green monkeys received a primary intranasal infection with RSV and were given a boost with RSV or a parainfluenza virus (PIV) vector expressing RSV fusion protein engineered for enhanced immunogenicity. The RSV boost was highly restricted but induced a significant increase in serum RSV-neutralizing antibodies. The PIV vectors replicated efficiently and induced significantly higher antibody responses. The use of an attenuated PIV vector expressing RSV antigen to boost a primary immunization with an attenuated...
Advances in RSV vaccine research and development – A global agenda
Vaccine, 2016
Highlights RSV is a significant annual cause of lower respiratory tract illness globally. Pediatric and elderly populations are most vulnerable, but no vaccine exists. The current state of RSV vaccine research and development is summarized. 60 RSV vaccine candidates in development, of which 16 are in Phase 1-3 trials.
Respiratory syncytial virus vaccine development
Current Opinion in Pediatrics, 2000
Development of an RSV vaccine for infants has been hindered by the lack of an ideal animal model that exhibits disease, and the challenge of effectively immunizing very young infants who are immunologically immature. Nevertheless, significant progress has been made recently in developing live attenuated viruses and protein subunit vaccine candidates. Numerous vaccine candidates are currently in early clinical trials. This paper reviews the significant obstacles to development of RSV vaccines, and the progress made to date.
Pathogenesis of RSV lower respiratory tract infection: implications for vaccine development
Vaccine, 2001
Respiratory syncytial virus (RSV) infection is the most prevalent cause of severe respiratory disease in infants. It also causes considerable morbidity in older children and adults with underlying risk factors. RSV vaccine development has been complicated by the need to administer the vaccine at a very young age and by enhanced disease observed after vaccination with formalin inactivated RSV. For infants live attenuated vaccines, which may not be expected to predispose for vaccine induced enhanced pathology, hold the greatest promise. However, the balance between attenuation and immunogenicity appears to be delicate. For older risk groups, results with subunit vaccines are most promising.
Respiratory syncytial virus (RSV) vaccines—Two steps back for one leap forward
Journal of Clinical Virology, 2008
Respiratory viruses are among the most important causes of morbidity and mortality worldwide. From a vaccine viewpoint, such viruses may be divided into two principle groups-those where infection results in long-term immunity and whose continued survival requires constant mutation, and those where infection induces incomplete immunity and repeated infections are common, even with little or no mutation. Influenza virus and respiratory syncytial virus (RSV) typify the former and latter groups, respectively. Importantly, successful vaccines have been developed against influenza virus. However, this is not the case for RSV, despite many decades of research and several vaccine approaches. Similar to natural infection, the principle limitation of candidate RSV vaccines in humans is limited immunogenicity, characterised in part by short-term RSV-specific adaptive immunity. The specific reasons why natural RSV infection is insufficiently immunogenic in humans are unknown but circumvention of innate and adaptive immune responses are likely causes. Fundamental questions concerning RSV/host interactions remain to be addressed at both the innate and adaptive immune levels in humans in order to elucidate mechanisms of immune response circumvention. Taking the necessary steps back to generate such knowledge will provide the means to leap forward in our quest for a successful RSV vaccine. Recent developments relating to some of these questions are discussed.