Serum and nasal wash antibodies associated with resistance to experimental challenge with influenza A wild-type virus

Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: 1) accelerates and enhances the specific antibody response induced by influenza vaccine; 2) allows for antigen sparing; and 3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain.

Section: Rov-asp-1 Induces a Stronger Th1-associated Influenza-specifsupporting

confidence: 49%

Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in aqueous formulation with influenza vaccines

Jiang

Fisher

Hensley

et al. 2014

“…Generally, vaccination by injection route elicits mostly humoral antibodies. Interestingly however, our results showed a high incidence (42%) of mucosal IgA response in rhesus monkeys compared to those induced by other inactivated virus vaccine in humans [15]. This increase in specific antibody production at the mucosa of the upper respiratory tract may be of importance for the prevention of SARS-CoV virus infection at its early stages, as the mucosal surfaces are the primary route of SARS transmission.…”

Section: Discussionmentioning

confidence: 48%

Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys

Zhou

Wang

Zhong

et al. 2005

An inactivated vaccine for severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was evaluated in rhesus monkeys. The monkeys were inoculated intramuscularly (i.m.) with 0.5, 5, 50, or 5000 microg of vaccine, or PBS as control, and boosted on day 7. After 3 weeks, they were challenged with the NS-1 strain of SARS-CoV. The humoral and mucosal immune responses, clinical signs, chemical indices and viremia were monitored following the immunization and challenge. The control animals who received PBS developed atypical SAR-CoV infection after viral challenge, according to clinical, virological and pathological findings. No systematic side effects were observed in vaccinated animals post-immunization, even in at the high dose of 5000 microg. The 50 microg dosage of vaccine elicited SARS-CoV specific immune responses against viral infection as compared to the partial immunity elicited by 0.5 and 5 microg doses. The results show that this inactivated vaccine can induce effective concomitant humoral and mucosal immunity against SARS-CoV infection, is safe in monkeys, and the vaccine maybe a good candidate for clinical trials.

“…Influenza viruses are singlestranded ribonucleic acid (RNA) viruses surrounded by a lipid containing envelope spiked with two glycoproteins: hemagglutinin (HA) and neuraminidase (NA). These glycoproteins, and HA, in particular, have been recognized as key antigens in the host response to influenza virus in both natural infection and vaccination [4,5]. The viruses are well known for their ability to mutate to circumvent immunity and re-infect the host.…”

Section: Introductionmentioning

confidence: 99%

Expression and purification of an influenza hemagglutinin—one step closer to a recombinant protein-based influenza vaccine

Wang¹,

Holtz²,

Anderson³

et al. 2006

126

Numerous human infections with avian influenza viruses in Asia in recent years have raised the concern that the next influenza pandemic is imminent. The most effective way to combat influenza is through the vaccination of the public. However, a minimum of 3-6 months is needed to develop an influenza vaccine using the traditional egg-based vaccine approach. The influenza hemagglutinin protein (HA), the active ingredient in the current vaccine, can be expressed in insect cells using the baculovirus expression vector system and purified rapidly. An influenza vaccine based on such a recombinant antigen allows a more timely response to a potential influenza pandemic. Here, we report an innovative monitoring assay for recombinant HA (rHA) expression and a rapid purification process. Various biochemical analyses indicate that the purified rHA is properly folded and biologically active.