Multivalent vaccines: Prospects and challenges

Re, Spier

doi:10.1007/bf02898716

Cited by 8 publications

(8 citation statements)

References 13 publications

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“…6 Beside immunologic interference, the other issues of the rational design of combination vaccine include the presence of preservatives, additives, or manufacturing residuals other than antigens. 1,5 For examples, adverse events have been associated with JEV vaccine due to the use of protamine sulfate during purification, the use of gelatin in freeze-drying, and/or the use of thimerosal in multi-dose containers. To lower the risk of postvaccination encephalitis as well as hypersensitivity reactions, JEV antigen used in our study was propagated in the cell culturebased technology and purified with Benzonase ® endonuclease.…”

Section: Discussionmentioning

confidence: 99%

“…Different antigens are merged into one vaccine formulation could be difficult to overcome chemical incompatibility and immunologic interference. 4,5 Regarding this, incorporation of vaccine adjuvants (Latin adjuvare, "to help") to vaccine candidates is a potential strategy to bypass these limitations. 6 Vaccine adjuvants are conferred on the substance that helps the host to elicit a robust and effective antigen-specific immune response.…”

Section: Introductionmentioning

confidence: 99%

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Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV

Lin

Chang

Chen³

et al. 2013

Human Vaccines & Immunotherapeutics

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Combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. Here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (H5N1/H1N1), enterovirus 71 (EV71), and/or Japanese encephalitis virus (JEV) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. We demonstrated that the antigenic competition happens between H5N1/H1N1 or H5N1/EV71 inactivated virions when the vaccine combinations either formulated with Alum suspensions or without adjuvant. In the presence of PELC emulsified particles, EV71-specific immune responses before and after incorporating H5N1 virus into EV71 vaccine were detected of no significant difference; in addition, H5N1- and EV71-specific immune responses were found at the same level when H5N1/EV71/JEV consolidating into combination vaccine. Emulsified vaccine formulation was represented as a potential tool that is found to reduce the number of injections required to prevent multiple infectious strains causing the same disease (H5N1/H1N1) and/or that protect against different diseases (H5N1/EV71). Combination vaccines can also include a third component to protect against H5N1/EV71/JEV at the same time.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV

Lin

Chang

Chen³

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Another advantage of using multivalent vaccine is that it allows generation of multiple peptides with varied MHC restriction. Since human population express a vast repertoire of MHC, a multivalent vaccine can generate a better and broader immune response in a human population than a single subunit vaccine that has limited MHC restriction [21,22]. Therefore, in this study we attempted to combine the three antigens (ALT-2, HSP12.6 and TSP-LEL) of B. malayi as a multivalent fusion vaccine and evaluated its vaccine potential ex vivo in human and in a mouse model.…”

Section: Introdcutionmentioning

confidence: 99%

Multivalent fusion protein vaccine for lymphatic filariasis

Dakshinamoorthy

Samykutty

Munirathinam

et al. 2013

Vaccine

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Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of Brugia malayi, heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of B. malayi L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against B. malayi L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human.

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“…This result further confirmed the effectiveness of the MuPyV VLP as an antigen delivery system, as evidenced by the high peptide‐specific antibody responses achieved using less than 600 ng of each peptide (see Materials and Methods Section), and without adjuvant. The lower titer specific to GAS3 may be due to immunological interference, by which one component in a vaccine formulation suppresses the immunogenicity of another component (Spier, ).…”

Section: Resultsmentioning

confidence: 99%

Microbially synthesized modular virus‐like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants

Chuan

Wibowo

Connors

et al. 2013

Biotech & Bioengineering

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Effective and low-cost vaccines are essential to control severe group A streptococcus (GAS) infections prevalent in low-income nations and the Australian aboriginal communities. Highly diverse and endemic circulating GAS strains mandate broad-coverage and customized vaccines. This study describes an approach to deliver cross-reactive antigens from endemic GAS strains using modular virus-like particle (VLP) and capsomere systems. The antigens studied were three heterologous N-terminal peptides (GAS1, GAS2, and GAS3) from the GAS surface M-protein that are specific to endemic strains in Australia Northern Territory Aboriginal communities. In vivo data presented here demonstrated salient characteristics of the modular delivery systems in the context of GAS vaccine design. First, the antigenic peptides, when delivered by unadjuvanted modular VLPs or adjuvanted capsomeres, induced high titers of peptide-specific IgG antibodies (over 1 × 10(4) ). Second, delivery by capsomere was superior to VLP for one of the peptides investigated (GAS3), demonstrating that the delivery system relative effectiveness was antigen-dependant. Third, significant cross-reactivity of GAS2-induced IgG with GAS1 was observed using either VLP or capsomere, showing the possibility of broad-coverage vaccine design using these delivery systems and cross-reactive antigens. Fourth, a formulation containing three pre-mixed modular VLPs, each at a low dose of 5 μg (corresponding to <600 ng of each GAS peptide), induced significant titers of IgGs specific to each peptide, demonstrating that a multivalent, broad-coverage VLP vaccine formulation was possible. In summary, the modular VLPs and capsomeres reported here demonstrate, with promising preliminary data, innovative ways to design GAS vaccines using VLP and capsomere delivery systems amenable to microbial synthesis, potentially adoptable by developing countries.

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Multivalent vaccines: Prospects and challenges

Cited by 8 publications

References 13 publications

Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV

Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV

Multivalent fusion protein vaccine for lymphatic filariasis

Microbially synthesized modular virus‐like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants

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