The role of nasal IgA in children vaccinated with live attenuated influenza vaccine.

Background: Immunoglobulin A (IgA) is the predominant antibody produced in response to mucosal infections. The role of IgA in providing protection against influenza in children vaccinated with live attenuated influenza vaccine (LAIV) has not been well described.

Methods: Nasal IgA responses were assessed using data from 3 prospective, 2-year, randomized studies comparing LAIV with placebo in children 6-36 months of age.

Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials.

Background: The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.

Methods/principal Findings: Two randomized, double-blind, placebo-controlled studies were completed in children (2-17 y) and adults (18-49 y). Subjects were assigned 4:1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart.

Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection.

Vacc-4x is being developed by Bionor Immuno AS as a therapeutic vaccine to be used in conjunction with antiretroviral therapies by individuals infected with HIV. The vaccine is comprised of four synthetic peptides describing sequences from within the highly conserved HIV core protein p24, which are thought to induce T-cell-mediated responses. Vacc-4x was assessed in 51 patients infected with HIV in one phase I and one phase II clinical trial and was demonstrated to be safe and generally well tolerated with no significant adverse events.

GSK's novel split-virus adjuvanted vaccines for the prevention of the H5N1 strain of avian influenza infection.

Although influenza pandemics occur infrequently, they are unpredictable. Given that humans had not been previously exposed to the novel H5N1 strain, few (if any) individuals have any degree of immunity to the strain. GlaxoSmithKline plc (GSK) has developed two inactivated split H5N1 vaccines adjuvanted with GSK's proprietary oil-in-water emulsion AS03: GSK-1562902A (produced in Dresden, Germany) and GSK-1557484A (produced in Québec, Canada).

IC-51, an injectable vaccine for the prevention of Japanese encephalitis virus infection.

The mosquito-borne Japanese encephalitis (JE) virus is the major etiological agent of viral encephalitis in children living in South-East Asia, causing comas, seizures and Parkinson's disease-like movement disorders. Travelers and military personnel visiting the region are also highly susceptible to the disease. As the population in South-East Asia increases, more land is irrigated to produce rice paddies (the ideal breeding habitat for mosquitoes), and pig breeding (a zoonotic host for mosquitoes) becomes more widespread.

IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection.

Bavarian Nordic is developing IMVAMUNE, which is based on a live attenuated modified vaccinia Ankara virus, for the potential prevention of smallpox infection, particularly in those patients contraindicated to traditional smallpox vaccines, such as the immunocompromised and those with eczema or dermatitis. In phase I and II clinical trials, IMVAMUNE was highly immunogenic and safe with no unexpected side effects or serious adverse effects reported in either healthy volunteers, those immunocompromised by HIV infection or in volunteers with atopic dermatitis. Additional phase II trials were ongoing in these groups at the time of publication and phase III trials were planned for 2009.

Intranasal Protollin-formulated recombinant SARS S-protein elicits respiratory and serum neutralizing antibodies and protection in mice.

The feasibility of developing a prophylactic vaccine against SARS was assessed by comparing the immune responses elicited by immunizing mice with a recombinant SARS spike glycoprotein (S-protein) formulated with different adjuvants, given by different routes. In both young and aged mice, an intranasal Protollin-formulated S-protein vaccine elicited high levels of antigen-specific IgG in serum, comparable to those elicited by an intramuscular Alum-adsorbed S-protein vaccine. Serum antibodies were shown to be virus neutralizing.

Intranasal proteosome-based respiratory syncytial virus (RSV) vaccines protect BALB/c mice against challenge without eosinophilia or enhanced pathology.

A safe and effective vaccine against respiratory syncytial virus (RSV) is still unavailable. Proteosome-based adjuvants are derived from the outer membrane proteins (OMP) of Neisseria species and are potent inducers of both mucosal and systemic immunity in humans and animals. Candidate RSV subunit vaccines comprising enriched RSV proteins (eRSV) formulated with proteosomes alone or with LPS (Protollin) were produced.

C57Bl/6 mice are protected from respiratory syncytial virus (RSV) challenge and IL-5 associated pulmonary eosinophilic infiltrates following intranasal immunization with Protollin-eRSV vaccine.

The protective efficacy of an intranasal (IN) Protollin-eRSV vaccine has recently been demonstrated in the RSV-susceptible BALB/c mouse model. Here, we report the safety, immunogenicity and efficacy of Protollin-eRSV vaccine in the relatively resistant C57Bl/6 mouse model. C57Bl/6 mice immunized IN with either two or three doses of Protollin-eRSV produced significant systemic and mucosal RSV-specific antibodies.

Safety and immunogenicity of a Proteosome -trivalent inactivated influenza vaccine, given nasally to healthy adults.

We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in normal, healthy adults. In a randomized, double-blind trial participants (n = 78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45 microg of each of the three HA antigens, or two nasal doses containing 30 microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule.

Intranasal Protollin/F1-V vaccine elicits respiratory and serum antibody responses and protects mice against lethal aerosolized plague infection.

F1-V is a recombinant plague antigen comprising the capsular (F1) and virulence-associated (V) proteins. Given intramuscularly with Alhydrogel, it protects mice against challenge, but is less effective in non-human primates against high-dose aerosolized Yersinia pestis challenge, perhaps because it fails to induce respiratory immunity. Intranasal immunization of mice with F1-V formulated with a Proteosome-based adjuvant (Protollin), elicited high titers of specific IgA in lungs whereas intranasal F1-V alone or intramuscular Alhydrogel-adsorbed F1-V did not.

Boostrix (GlaxoSmithKline).

GlaxoSmithKline plc has developed and launched Boostrix, a subunit vaccine for use in adolescents and adults as a booster immunization against diphtheria, tetanus and pertussis (DTPa) infections.

Peru-1 5 (AVANT).

Peru-15 is a single dose, recombinant cholera vaccine under development by AVANT Immunotherapeutics for the potential prevention of cholera. A phase II trial of Peru-15 was ongoing in June 2003, and as of September 2003 AVANT was planning a phase III trial in a developing country, and phase IIb and phase III challenge studies in travelers.

Technology evaluation: ChimeriVax-DEN, Acambis/Aventis.

Acambis, in collaboration with Aventis Pasteur, is developing a chimeric vaccine based on a recombinant yellow fever vaccine for the potential prevention of dengue virus infection. The vaccine is undergoing phase I clinical trials.

Protollin: a novel adjuvant for intranasal vaccines.

Protollin is a novel adjuvant comprising Proteosomes non-covalently complexed with LPS. Intranasal immunization of mice with Protollin combined with detergent-split influenza antigens (HA) or recombinant influenza hemagglutinin (rHA) enhanced serum IgG and mucosal IgA levels by up to 250-fold compared with immunization with the antigens alone. IFN-gamma responses were also enhanced compared to the levels produced by splenocytes from mice immunized with antigen alone, while production of IL-5 was abrogated.

A chimeric live attenuated vaccine against Japanese encephalitis.

Japanese encephalitis is a disease of the CNS, endemic in Asia and Oceania. The disease is refractory to drug treatments and whilst the rural economies remain heavily dependent on agriculture, conditions for propagation of the disease will persist. Thus, there is a need for effective vaccines.

ChimeriVax-JE. Acambis.

Acambis (formerly Peptide Therapeutics Group) is developing a vaccine for the potential prophylaxis of Japanese encephalitis (JE) virus infections. In August 2001, Acambis commenced a phase II trial of its ChimeriVax-JE vaccine; these studies were complete by February 2002 and the company was making plans to begin an additional phase II study in children living in areas where JE is prevalent. By May 2003, Acambis had initiated a phase II trial in Australia.

A nasal Proteosome influenza vaccine containing baculovirus-derived hemagglutinin induces protective mucosal and systemic immunity.

The potential for enhancing the immunogenicity of recombinant (baculovirus-derived) influenza hemagglutinin (rHA) was investigated by comparing the immune responses elicited in mice by an intranasal (i.n.) rHA formulated with Proteosomes, with those induced by intramuscular (i.

Resiquimod 3M.

3M Pharmaceuticals is developing a topical formulation of resiquimod as an immunomodulator for the potential treatment of herpes simplex virus (HSV) infections. As of September 2001, resiquimod was to be commercialized worldwide in association with Eli Lilly. Phase III trials for the treatment of HSV infection were initiated in November 2000 and were ongoing in September 2001.

Hepagene (PowderJect).

Celltech Group (formerly Medeva) developed Hepagene, a recombinant polyvalent vaccine with potential activity against hepatitis B virus infections [353474]. In September 2000, PowderJect acquired the product as part of its acquisition of Celltech's vaccine manufacturing business [381557]. In July 2001, PowderJect reported that evaluation was nearing completion.

Remune. Immune Response.

The Immune Response Corp (IRC) is developing Remune, a potential HIV therapeutic vaccine. Remune is based on the Salk Immunogen, which is derived from an HIV isolate which has been inactivated by chemical depletion of glycoprotein 120 (gp120). Preliminary data suggested that Remune, in combination with antiviral drug therapy, results in undetectable levels of HIV.

Varivax (Merck & Co).

Varivax is a live-attenuated varicella vaccine developed and launched in the US by Merck & Co for the treatment of chickenpox [413319]. The vaccine uses the Oka strain of the varicella virus licensed from the Biken Institute at Osaka University in Japan [178223]. By June 2001, Merck was also developing the vaccine for use in adults for herpes zoster infection [413319].