Safety and immunogenicity of a bivalent norovirus vaccine candidate in infants from 6 weeks to 5 months of age: A phase 2, randomized, double-blind trial.

As infants suffer significant morbidity and mortality due to norovirus-related acute gastroenteritis (AGE), we assessed four formulations of the bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in Panamanian and Colombian infants. 360 infants aged 6 weeks to 5 months were randomly allocated to 8 groups to receive three doses of HIL-214 or two doses of HIL-214 and one dose of placebo (Days 1, 56 and 112), where HIL-214 doses contained 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.

Efficacy of an intramuscular bivalent norovirus GI.1/GII.4 virus-like particle vaccine candidate in healthy US adults.

Background: We performed this first-in-human efficacy trial of Takeda's bivalent norovirus vaccine candidate (TAK-214) against moderate or severe acute gastroenteritis (AGE) in healthy adults.

Methods: This double-blind, randomized, placebo-controlled phase 2b trial was conducted over two winter seasons in 18-49 year-old US Navy recruits. Participants were randomized (1:1) to receive intramuscular injections of saline placebo (N = 2,357) or TAK-214 [15 μg GI.

An Exploratory Study of the Salivary Immunoglobulin A Responses to 1 Dose of a Norovirus Virus-Like Particle Candidate Vaccine in Healthy Adults.

As noroviruses are transmitted through the fecal-oral route, we investigated humoral and mucosal (salivary immunoglobulin A [IgA]) immune responses in a phase 2 trial of Takeda's bivalent norovirus virus-like particle (VLP) vaccine candidate in 50 healthy 18- to 49-year-olds. The vaccine had an acceptable tolerability profile and induced rapid, robust humoral immune responses after 1 intramuscular dose of vaccine candidate. Seroresponses were evident 8 days after vaccination as panimmunoglobulin, IgA, and histo-blood group antigen-blocking antibodies against both vaccine GI.

Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial.

Background: We investigated safety and immunogenicity of 1-2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18- to 64-year-olds.

Methods: On days 1 and 28, participants (n = 420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and GII.

Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination.

Background: Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.

B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine.

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the first identified correlate of protection from HuNoV gastroenteritis. Recently, virus-specific IgG memory B cells were identified to be another potential correlate of protection against HuNoV gastroenteritis.

Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial.

Background: Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18-49 years.

Methods: Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 µg or 50 µg of GI.

Serological Correlates of Protection against a GII.4 Norovirus.

Noroviruses are the leading cause of acute gastroenteritis worldwide, and norovirus vaccine prevention strategies are under evaluation. The immunogenicity of two doses of bivalent genogroup 1 genotype 1 (GI.1)/GII.

Broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus VLP candidate vaccine: immunological analyses from a phase I clinical trial.

Background: Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity.

Robust mucosal-homing antibody-secreting B cell responses induced by intramuscular administration of adjuvanted bivalent human norovirus-like particle vaccine.

Background: Two major antigenically heterogenous norovirus genogroups (GI and GII) commonly infect humans and are the leading cause of foodborne, viral gastrointestinal infections in adults.

Methods: We assessed B cell responses in participants in a double-blind, placebo-controlled, dose-escalation phase 1 study of the safety and immunogenicity of an intramuscular bivalent norovirus virus-like particle (VLP) vaccine. The vaccine contained a GI.

Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.

Background: Vaccines against norovirus, the leading cause of acute gastroenteritis, should protect against medically significant illness and reduce transmission.

Methods: In this randomized, double-blind, placebo-controlled trial, 18- to 50-year-olds received 2 injections of placebo or norovirus GI.1/GII.

A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults.

Background: Noroviruses are the most important viral causes of gastroenteritis-related morbidity and mortality. A randomized, double-blind, placebo-controlled study evaluated an adjuvanted bivalent intramuscular norovirus virus-like particle (VLP) vaccine.

Methods: Forty-eight adults aged 18-49 years received either 2 doses containing genotype GI.

Needle-free jet injection for administration of influenza vaccine: a randomised non-inferiority trial.

Background: Administration of vaccines by needle-free technology such as jet injection might offer an alternative to needles and syringes that avoids the issue of needle phobia and the risk of needle-stick injury. We aimed to assess the immunogenicity and safety of trivalent influenza vaccine given by needle-free jet injector compared with needle and syringe.

Methods: For this randomised, comparator-controlled trial, we randomly assigned (1:1) healthy adults (aged 18-64 years) who attended one of four employee health clinics in the University of Colorado health system, with stratification by site, to receive one dose of the trivalent inactivated influenza vaccine Afluria given either intramuscularly with a needle-free jet injector (Stratis; PharmaJet, Golden, CO, USA) or with needle and syringe.

Norovirus virus-like particle vaccines for the prevention of acute gastroenteritis.

Noroviruses (NoVs) are the most common cause of nonbacterial acute gastroenteritis in humans worldwide. These highly infectious viruses were, until recently, commonly thought to cause a mild, self-limiting disease in healthy individuals, but increasing epidemiology shows that the incidence and severity of illness due to NoV infection is substantial and similar to diseases where immunization is widely recommended. Human NoV challenge studies have identified carbohydrate histo-blood group antigen expression as an important human susceptibility factor for many strains and correspondingly, that antibodies which block carbohydrate virus binding represent a potential correlate of protection against NoV infection and illness.

Norovirus vaccine against experimental human Norwalk Virus illness.

Background: Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection.

Methods: We conducted a randomized, double-blind, placebo-controlled, multicenter trial to assess the safety, immunogenicity, and efficacy of an investigational, intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis after challenge with a homologous viral strain, Norwalk virus (genotype GI.

Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

Background: Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide.

Methods: We conducted 2 phase 1 double-blind, controlled studies of a virus-like particle (VLP) vaccine derived from norovirus GI.1 genotype adjuvanted with monophosphoryl lipid A (MPL) and the mucoadherent chitosan.

Safety and immunogenicity of concurrent administration of live attenuated influenza vaccine with measles-mumps-rubella and varicella vaccines to infants 12 to 15 months of age.

Objective: This study evaluated the safety, tolerability, and immunogenicity of live attenuated influenza vaccine administered concurrently with measles-mumps-rubella vaccine and varicella vaccine to healthy children 12 to 15 months of age.

Methods: Children were assigned randomly to receive (1) measles-mumps-rubella vaccine, varicella vaccine, and intranasal placebo on day 0, followed by 1 dose of live attenuated influenza vaccine on days 42 and 72; (2) measles-mumps-rubella, varicella, and live attenuated influenza vaccines on day 0, followed by a second dose of live attenuated influenza vaccine on day 42 and intranasally administered placebo on day 72; or (3) 1 dose of live attenuated influenza vaccine on days 0 and 42, followed by measles-mumps-rubella and varicella vaccines on day 72. Serum samples were collected before vaccination on days 0, 42, and 72.

Medical burden of respiratory syncytial virus and parainfluenza virus type 3 infection among US children. Implications for design of vaccine trials.

Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are two leading causes of lower respiratory illness (LRI) in infants. Many efforts have been directed to develop vaccines against these two viruses. Licensure of new vaccines includes three phases of clinical trials to evaluate safety, immunogenicity, and efficacy.

A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.

Background: Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent vaccine containing cold-adapted influenza vaccine viruses that infect and replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses is not equated with transmission because transmission requires more virus than is detected in many nasal swabs.

A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy.

Background: A phase 2 trial was conducted to assess in young infants the safety, tolerability, infectivity, and immunogenicity of multiple doses of an intranasal vaccine using bovine parainfluenza virus type 3 (bPIV3).

Methods: One hundred ninety-two healthy 2-month-old infants were randomized 1 : 1 : 1 to receive 1x10(5) median tissue culture infective dose (TCID(50)) bPIV3 vaccine, 1x10(6) TCID(50) bPIV3 vaccine, or placebo at 2, 4, 6, and 12-15 months of age. Safety information was collected by use of diary sheets and telephone interviews.

Safety, immunogenicity and efficacy of intranasal, live attenuated influenza vaccine.

Data supporting the use of the live attenuated influenza vaccine (LAIV) in children and adults is reviewed, and the development and characteristics of the vaccine are summarized. The vaccine is highly effective and well tolerated in children and adults from 5 to 49 years of age. Correlates of immune protection include serum hemagglutination-inhibition antibody and secretory immunoglobulin A.

Live attenuated influenza vaccine induces cross-reactive antibody responses in children against an a/Fujian/411/2002-like H3N2 antigenic variant strain.

Serum antibody titers against the A/Panama/2007/99(H3N2) and A/Fujian/411/2002(H3N2)-like viruses were determined in children 6-35 months of age who received either 1 dose of the inactivated influenza vaccine or the live attenuated influenza vaccine containing the A/Panama strain. Results indicated that the live vaccine induced higher antibody responses than the inactivated vaccine against the A/Panama and A/Fujian-like viruses.