Progress in the development of human parainfluenza virus vaccines

Schmidt, Alexander; Schaap-Nutt, Anne; Bartlett, Emmalene J.; Schomacker, Henrick; Boonyaratanakornkit, Jim; Karron, Ruth A.; Collins, Peter L.

doi:10.1586/ers.11.32

Cited by 105 publications

(98 citation statements)

References 99 publications

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“…Currently, there are no vaccines for RSV or HPIV, although research is underway (18,54,55). Our work could aid in timing vaccination to make optimal use of interference.…”

Section: Discussionmentioning

confidence: 99%

Cross-immunity between strains explains the dynamical pattern of paramyxoviruses

Bhattacharyya

Gesteland

Korgenski

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Viral respiratory tract diseases pose serious public health problems. Our ability to predict and thus, be able to prepare for outbreaks is strained by the complex factors driving the prevalence and severity of these diseases. The abundance of diseases and transmission dynamics of strains are not only affected by external factors, such as weather, but also driven by interactions among viruses mediated by human behavior and immunity. To untangle the complex out-ofphase annual and biennial pattern of three common paramyxoviruses, Respiratory Syncytial Virus (RSV), Human Parainfluenza Virus (HPIV), and Human Metapneumovirus (hMPV), we adopt a theoretical approach that integrates ecological and immunological mechanisms of disease interactions. By estimating parameters from multiyear time series of laboratory-confirmed cases from the intermountain west region of the United States and using statistical inference, we show that models of immune-mediated interactions better explain the data than those based on ecological competition by convalescence. The strength of cross-protective immunity among viruses is correlated with their genetic distance in the phylogenetic tree of the paramyxovirus family.paramyxoviruses | respiratory syncytial viruses | human parainfluenza | pathogen interactions | cross-immunity

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“…Currently, there are no vaccines for RSV or HPIV, although research is underway (18,54,55). Our work could aid in timing vaccination to make optimal use of interference.…”

Section: Discussionmentioning

confidence: 99%

Cross-immunity between strains explains the dynamical pattern of paramyxoviruses

Bhattacharyya

Gesteland

Korgenski

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Formalin-inactivated HRSV and HPIV vaccines in the 1960s were poorly protective, and the formalin-inactivated HRSV vaccine primed for enhanced disease after subsequent HRSV infection (4,5). Parallel strategies for HRSV and HPIV vaccines have continued during the past 5 decades, and over the last 20 years, the field has largely focused on developing live attenuated vaccines delivered to the respiratory mucosa for the pediatric population (1,2,6). It is possible that prefusion F protein in its native structure may be superior to previously failed subunit vaccines (7,8), although such a vaccine might be expected, at least at first, to be best targeted to the elderly and pregnant mothers.…”

mentioning

confidence: 99%

Relationships among Dissemination of Primary Parainfluenza Virus Infection in the Respiratory Tract, Mucosal and Peripheral Immune Responses, and Protection from Reinfection: a Noninvasive Bioluminescence-Imaging Study

Burke

Hurwitz

et al. 2015

J Virol

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Respiratory paramyxoviruses such as respiratory syncytial virus (RSV) and human parainfluenza virus type 1 (HPIV1) to HPIV4 infect virtually all children by the age of 2 to 5 years, leading to partial but incomplete protection from reinfection. Here, we used luciferase-expressing reporter Sendai viruses (the murine counterpart of HPIV1) to noninvasively measure primary infection, immune responses, and protection from reinfection by either a lethal challenge or natural transmission in living mice. Both nonattenuated and attenuated reporter Sendai viruses were used, and three inoculation strategies were employed: intramuscular (i.m.), intranasal (i.n.) at a low dose and low volume, and i.n. at a high dose and high volume. High-dose, high-volume i.n. inoculation resulted in the highest levels of antibody responses and protection from reinfection. Low-dose, low-volume i.n. inoculation afforded complete protection from contact transmission and protection from morbidity, mortality, and viral growth during lethal challenge. i.m. inoculation was inferior to i.n. inoculation at inducing antibody responses and protection from challenge. For individual mice and across groups, the levels of serum binding and neutralizing antibody responses correlated with primary infection and protection from reinfection in the lungs. Contact transmission, the predominant mode of parainfluenza virus transmission, was modeled accurately by direct i.n. inoculation of Sendai virus at a low dose and low volume and was completely preventable by i.n. vaccination of an attenuated virus at a low dose and low volume. The data highlight differences in infection and protection from challenge in the upper versus lower respiratory tract and bear upon live attenuated vaccine development. IMPORTANCEThere are currently no licensed vaccines against HPIVs and human RSV (HRSV), important respiratory pathogens of infants and children. Natural infection leads to partial but incomplete protective immunity, resulting in subsequent reinfections even in the absence of antigenic drift. Here, we used noninvasive bioluminescence imaging in a mouse model to dissect relationships among (i) the mode of inoculation, (ii) the dynamics of primary infection, (iii) consequent immune responses, and (iv) protection from high-dose, high-volume lethal challenge and contact transmission, which we find here to be similar to that of a mild low-dose, low-volume upper respiratory tract (URT)-biased infection. Our studies demonstrate the superiority of i.n. versus i.m. vaccination in protection against both lethal challenge and contact transmission. In addition to providing correlates of protection that will assist respiratory virus vaccine development, these studies extend the development of an increasingly used technique for the study of viral infection and immunity, noninvasive bioluminescence imaging.H uman respiratory syncytial virus (HRSV), human metapneumovirus (HMPV), and human parainfluenza virus type 1 (HPIV1) to HPIV4 are leading viral causes of pediatric hospitaliza...

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“…In other trials, a recombinant form of the vaccine (rHPIV3cp45), re-derived from cDNA, shows a shorter passage time and reduced the risk of contamination or reversion 108 . It has been used in a phase 1 study of 40 seronegative children between 6-35 months and generates virus-specific antibodies with a tolerable safety profile 109 .…”

Section: Rsv Vaccine Developmentmentioning

confidence: 99%

“…Another trial utilizing rHPIV3cp45 in healthy young seronegative infants between 6-12 months demonstrated strong immunogenicity. These studies involved the delivery of multiple doses of vaccine with appropriate intervals which is necessary to sustain durable immune responses and children in particular are likely to benefit from the nasal route of administration due to the ability to generate protective mucosal and systemic immunity 108 .…”

Section: Rsv Vaccine Developmentmentioning

confidence: 99%