Plaque reduction neutralization test for measles antibodies: Description of a standardised laboratory method for use in immunogenicity studies of aerosol vaccination.
ABSTRACT Clinical trials of measles vaccination administered as aerosol are planned with the aim of obtaining licensure. Measles antibody levels will be measured using the plaque reduction neutralization test (PRNT) to assess antibody responses as a surrogate marker of efficacy.
A working group examined laboratory protocols for measles PRNT in use at three reference centres and agreed to a standardised procedure, which was subsequently validated.
Assay validation showed quantitative results varied approximately threefold both within and between assays. The lower limit of detection was approximately 20milliInternational Units/mL.
A standardised laboratory protocol for measles PRNT was established and validated for use in clinical trials of aerosolized measles vaccines.
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ABSTRACT: Background: There have been no reported studies involving aerosol immunization with 2 of the 3 components of MMR II vaccine—Attenuvax measles vaccine and Jeryl-Lyn mumps vaccine. Objective: To evaluate the safety and antibody responses to aerosolized Attenuvax measles strain, Jeryl Lynn mumps strain and RA 27/3 rubella component of an MMR vaccine in adults, before assessing the booster administration of this vaccine in children. Methods: A pilot study to evaluate safety and antibody responses of MMR II (Merch Sharp & Dhome Corp., Whitehouse Station, NJ 08889, USA) components administered by aerosol was carried out in 27 healthy adults of 21 to 38 years of age. All par-ticipants were followed-up during 28 days following immunization for detection of clinical adverse events. Immune response was evaluated by plaque reduction neutralization test for measles, and commercial ELISA kits for rubella and mumps. Results: Only mild clinical adverse events were noted. Despite high levels of baseline seropositivity to all vac-cine components, seroresponses to measles, rubella and mumps occurred in 44%, 15% and 41%, respectively. Conclu-sions: These outcomes compare favorably with earlier studies of other MMR vaccines given by aerosol. Further evalua-tions on safety and booster immune response should be performed in children.
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ABSTRACT: Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.Biologicals 07/2014; · 1.41 Impact Factor
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ABSTRACT: Measles is a highly infectious respiratory disease which causes 122,000 deaths annually. Although measles vaccine is extremely safe and effective, vaccine coverage could be improved by a vaccine that is more easily administered and transported. We developed an inhalable dry powder measles vaccine (MVDP) and two delivery devices, and demonstrated safety, immunogenicity, and efficacy of the vaccine in preclinical studies. Here we report the first clinical trial of MVDP delivered by inhalation. Sixty adult males aged 18 to 45 years, seropositive for measles antibody, were enrolled in this controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive either MVDP by Puffhaler(®) or by Solovent™ devices or the licensed subcutaneous measles vaccine. Adverse events (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followed for 180 days post-vaccination to assess potential serious long term adverse events. Measles antibody was measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaque reduction neutralization test. All subjects completed the study according to protocol. Most subjects had high levels of baseline measles antibody. No adverse events were reported. MVDP produced serologic responses similar to subcutaneous vaccination. MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibody titer which limited ability to measure the serologic responses, and may have limited the adverse events following vaccination. Additional studies in subjects without pre-existing measles antibody are needed to further elucidate the safety and immunogenicity of MVDP. Copyright © 2014 Elsevier Ltd. All rights reserved.Vaccine 11/2014; 32(50):6791-7. · 3.49 Impact Factor