Clinical Trial of Inhaled Aerosol of Human Diploid and Chick Embryo Measles Vaccines

Sabin, Albert B.; Castro, J Fernández de; Aréchiga, Amador Flores; Sever, JohnL.; Madden, D L; Shekarchi, Isabel C.

doi:10.1016/s0140-6736(82)90673-0

Cited by 20 publications

(6 citation statements)

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“…Even though aerosol delivery of live-attenuated MV vaccine offers promise, 38 , 43 , 44 clinical studies in children have produced variable results. Although effective in inducing secondary immune responses as booster vaccination, 45 primary vaccination of infants proved inferior to vaccination by standard injection, 13 , 46 , 47 contradictory to the results we obtained in non-human primates.…”

Section: Discussionmentioning

confidence: 99%

Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

et al. 2017

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Needle-free measles virus vaccination by aerosol inhalation has many potential benefits. The current standard route of vaccination is subcutaneous injection, whereas measles virus is an airborne pathogen. However, the target cells that support replication of live-attenuated measles virus vaccines in the respiratory tract are largely unknown. The aims of this study were to assess the in vivo tropism of live-attenuated measles virus and determine whether respiratory measles virus vaccination should target the upper or lower respiratory tract. Four groups of twelve cynomolgus macaques were immunized with 104 TCID50 of recombinant measles virus vaccine strain Edmonston-Zagreb expressing enhanced green fluorescent protein. The vaccine virus was grown in MRC-5 cells and formulated with identical stabilizers and excipients as used in the commercial MVEZ vaccine produced by the Serum Institute of India. Animals were immunized by hypodermic injection, intra-tracheal inoculation, intra-nasal instillation, or aerosol inhalation. In each group six animals were euthanized at early time points post-vaccination, whereas the other six were followed for 14 months to assess immunogenicity and protection from challenge infection with wild-type measles virus. At early time-points, enhanced green fluorescent protein-positive measles virus-infected cells were detected locally in the muscle, nasal tissues, lungs, and draining lymph nodes. Systemic vaccine virus replication and viremia were virtually absent. Infected macrophages, dendritic cells and tissue-resident lymphocytes predominated. Exclusive delivery of vaccine virus to the lower respiratory tract resulted in highest immunogenicity and protection. This study sheds light on the tropism of a live-attenuated measles virus vaccine and identifies the alveolar spaces as the optimal site for respiratory delivery of measles virus vaccine.

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Section: Discussionmentioning

confidence: 99%

Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

et al. 2017

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“…In addition, complacency, concerns about safety, and philosophical and religious objections to vaccination have resulted in a resurgence of measles in many industrialized nations (43, 102,130,145,151). Delivery by inhalation rather than needle and syringe has been proposed to help improve coverage (56,84,120), and both aerosol and dry powder versions of the EZ vaccine are in development for use both for use in primary immunization of infants and for delivery of the second dose to older children (18,34,52,56,76,78,84,150).…”

Section: Vaccine Delivery and Control Of Measles Transmissionmentioning

confidence: 99%

Measles Vaccine

Griffin

2018

Viral Immunology

100

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Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.

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“…However, nothing is known about the cells in which the vaccine virus replicates in vivo. With renewed interest in developing alternative vaccination routes, particularly aerosol vaccination (16,17), this information is of crucial importance.…”

mentioning

confidence: 99%

Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

Rennick

Vries

Carsillo

et al. 2015

J Virol

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Although live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston-Zagreb ( IMPORTANCE Even though MV strain Edmonston-Zagreb has long been used as a live-attenuated vaccine (LAV) to protect against measles, nothing is known about the primary cells in which the virus replicates in vivo.This is vital information given the push to move toward needle-free routes of vaccination, since vaccine virus replication is essential for vaccination efficacy. We have generated a number of recombinant MV strains expressing enhanced green fluorescent protein. The virus that best mimicked the nonrecombinant vaccine virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious.

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Clinical Trial of Inhaled Aerosol of Human Diploid and Chick Embryo Measles Vaccines

Cited by 20 publications

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Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

Measles Vaccine

Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

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