The new nano-complex,Hep-c,improves the immunogenicity of the hepatitis B vaccine

Prevention of hepatitis B requires a vaccine that stimulates the humoral and cellular immune responses in a balanced manner, particularly those associated with Th1 and cytotoxic T cells. Alum adjuvant is currently used in the hepatitis B vaccine formulations but it lacks the efficiency of establishing such immune responses. Therefore, for accessing a suitable vaccine to prevent this fatal disease, it is essential to design and construct a new adjuvant which can overcome the limitations of the alum adjuvant and can stimulate a strong Th1 response as used along with it. In the present study, the adjuvant effect of Hep-c, the first nano-complex which was synthesized by nanochelating technology to improve the immunogenicity of the vaccine against hepatitis B, had been evaluated.     

Platycodin D is a potent adjuvant of specific cellular and humoral immune responses against recombinant hepatitis B antigen

The ideal adjuvants for hepatitis B vaccines should be capable of eliciting both strong humoral and cellular immune responses, especially Th1 cell and cytotoxic T lymphocyte (CTL) responses. However, Alum used as adjuvants in the hepatitis B vaccines currently commercialized offers limitation in inducing cell-mediated response. Therefore, a less hemolytic saponin platycodin D (PD) from the root of Platycodon grandiflorum has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with Alum, antigen-specific cellular and humoral immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with PD and Alum in mice. The Con A-, LPS-, and HBsAg-induced splenocyte proliferation and the serum HBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody titers in the HBsAg-immunized mice were significantly enhanced by PD (P < 0.05, P < 0.01 or P < 0.001). PD also significantly promoted the production of Th1 (IL-2 and IFN-γ) and Th2 (IL-10) cytokines and up-regulated the mRNA expression of Th1 cytokines (IL-2 and IFN-γ) in splenocytes from the mice immunized with HBsAg (P < 0.001). Besides, PD remarkably increased the killing activities of natural killer (NK) cells and CTLs from splenocytes in the HBsAg-immunized mice (P < 0.001), which may have important implications for vaccination against hepatitis B virus. The results indicated that PD has strong potential to increase both cellular and humoral immune responses and elicit a balanced Th1/Th2 response against HBsAg, and that PD may be the candidates as adjuvants for use in prophylactic and therapeutic hepatitis B vaccine.     

RLJ-NE-299A: a new plant based vaccine adjuvant

Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40 microg) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 microg/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too.     

A hepatitis B vaccine formulated with a novel adjuvant system

Although more than 95% of the vaccinated population responds to the currently licensed vaccines against hepatitis B, some groups were found to be low responders. Lipid A as adjuvant, through its ability to activate macrophages, might improve humoral as well as cellular immune response. Therefore we evaluated the profile of a hepatitis B vaccine with the new adjuvant system SBAS4. 150 young adults were enrolled and randomized into three groups: one received the SBAS4 hepatitis B vaccine, the second Engerix-B(TM) and the third a hepatitis B vaccine with an alternative formulation on alum. Vaccinations were at 0 and 6 months. The vaccine was well tolerated. At month 7 all vaccinees were protected but with significant differences in GMTs between groups: 13,271 mIU/ml for the SBAS4 group versus 1203 and 1823 mIU/ml. Hence the hepatitis B vaccine with the new adjuvant system is more immunogenic compared to the other vaccines containing the same antigen and could be suitable for a two dose schedule.     

Comparison of AS03 and Alum on immune responses elicited by A/H3N2 split influenza vaccine in young,mature and aged BALB/c mice

IntroductionThere is great interest in developing more effective influenza vaccines for the elderly. Oil-in-water adjuvants can boost humoral responses to seasonal vaccines in elderly subjects but relatively little is known about their mechanism of action.MethodsWe compared humoral and cellular immune profiles in young adult (2 months), mature (11–12 months) or aged (16–17 month) female BALB/c mice following two doses of Alum or AS03-adjuvanted A/H3N2 split-virus antigen (A/Uruguay/716/2007) at 0.75 or 3 μg hemagglutinin (HA) per dose intramuscularly versus 3 μg HA without adjuvant.ResultsOverall, hemagglutination inhibition (HAI), microneutralization (MN) and end-point ELISA titres were higher in the young mice and when an adjuvant was used. Both adjuvants increased humoral responses in older animals but the highest titres across all groups were observed in the AS03-adjuvanted groups. Neither IgG avidity nor A/H3N2-specific splenocyte proliferation was influenced by age, antigen dose or adjuvant. In contrast, cytokine production by ex vivo-stimulated splenocytes differed widely between groups. Most cytokine levels in older mice vaccinated with antigen alone (3 μg HA/dose) were ≤50% of those in young animals. In young mice, cytokine levels increased modestly with Alum and significantly with AS03. Increases tended to be greatest at the lower antigen dose (0.75 μg versus 3 μg HA). In the older animals, Alum had little impact on cytokine production but responses in the AS03 groups paralleled those of the young mice (broad activation of Th1, Th2, and Th17-type cytokines) and the greatest increases were seen with the higher antigen dose (3 μg HA).ConclusionsIn both young and aged mice, Alum and AS03 increased the magnitude of humoral and cellular responses to split influenza virus vaccination. Overall, these effects were most pronounced in the younger animals and the groups receiving AS03. These data support the use of oil-in-water adjuvants in influenza vaccines targeting the elderly.     

Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii

The search for an effective vaccine against toxoplasmosis remains a challenging and elusive goal. Combination of epitopes from different stages of Toxoplasma gondii life cycle is an optimal strategy to overcome the antigen complexity of the parasite. Based on published epitope derived from several promising candidate vaccine antigens, we construct a DNA vaccine encoding multi-epitope of T. gondii and CpG motif, with or without the A2/B subunit of cholera toxin as a genetic adjuvant. The immunity induced by this vaccine in BALB/c mice and the protection afforded against challenge with the highly virulent RH strain of T. gondii is assessed. This vaccine was able to elicit a significant humoral and cellular immune response in vaccinated mice. Furthermore, CTXA2/B as a genetic adjuvant could enhance the magnitude of immune responses as well as increased survival rate in mice infected with the lethal RH tachyzoites. This study is the first report of a multi-epitope DNA construct strategy as a potential DNA vaccine against toxoplasmosis.     

Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

乙型肝炎疫苗与婴儿期常用疫苗同时接种的免疫应答与反应观察:Ⅱ.乙型肝炎疫苗与乙型脑炎、麻疹疫苗同时接种的免疫应答与反应观察

本文对HBV与JEV、MV同时接种的免疫应答性和反应作了研究。对0~9月龄215名婴儿随机分为Ⅰ组单独接种HBV,Ⅱ组分别接种JEV、MV,Ⅲ组HBV分别与MV、JEV同时接种,三针间隔为0、1、5个月。均作免前和免后的血清抗体测定,同时接种组的抗-HBs,JEV抗体的阳转率,GMT与单独接种无显著性差异,JEV抗体低于常规接种,MV的免疫应答性Ⅲ组低于Ⅱ组,有显著性差异。未见异常反应,一般反应均很轻微,二组间无差别,说明MV不宜与HBV同时接种,JEV不能用HBV免疫程序同时接种。     

Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection

Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.     

乙型肝炎疫苗与婴儿期常用疫苗同时接种的免疫应答与反应观察:Ⅰ.乙型肝炎疫苗与白百破混合疫苗、脊髓灰质炎活疫苗同时接种的免疫应答与反应观察

本文对HB疫苗与DPT、TOPV疫苗同时接种的免疫应答性作了研究。对0~5月龄的229名婴儿随机分为Ⅰ组单独接种HB疫苗,Ⅱ组接种DPT、TOPV疫苗,Ⅲ组HB疫苗与DPT、TOPV同时接种。三针间隔为0、1、5个月,均作免前和第三针后一个月的血清抗体测定,同时接种组的抗-HBs、白喉、破伤风、百日咳及Ⅰ、Ⅱ、Ⅲ型OPV抗体的阳转率、GMT与单独接种组无差别。未见异常反应,一般反应均很轻微,二组间无差别。表明上述几种疫苗同时接种是安全和有效的。     

Formulation of the prefusion RSV F protein with a Th1/Th2-balanced adjuvant provides complete protection without Th2-skewed immunity in RSV-experienced young mice

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants with most infections occurring in the first year of life. Multiple RSV exposures are required for children to mount adult-like immune responses. Although adult RSV immunity is associated with less severe disease, the protection induced through natural infection is short-lived. Therefore, vaccination of RSV-experienced young children may accelerate immunity and provide long-term protection from RSV reinfection. However, the extent to which different Th-biased vaccine regimens influence pre-existing humoral and cellular immunity in RSV-experienced young children is unknown. To address this question, infant BALB/c mice were RSV-infected and subsequently immunized with the prefusion RSV F (PreF) antigen formulated with either a Th2-skewing (Alum) or Th1/Th2-balanced (Advax-SM) adjuvant. These studies show that both adjuvants boosted neutralizing antibody and protected from RSV reinfection, but Advax-SM adjuvant prevented the Th2-skewed immunity observed in RSV-experienced young mice immunized with PreF/Alum.     

乙型肝炎疫苗与儿期常用疫苗同时接种的免疫应答与反应观察Ⅲ．乙型肝炎疫苗与卡介苗、A群流脑多糖菌苗同时接种的免疫应答与反应观察

本文对HBV与BCG、BAPV同时接种的免疫应答性和接种反应作了研究，对出生3天内的360名新生婴儿，随机分为I组单独接种三针10μgHBV，Ⅱ组分别接种BCGs及50μg MAPV，Ⅲ组HBV分别与BCGs、MAPV同时接种，Ⅳ组分别接种BCGi和MAPV，Ⅴ组HBV分别与BCGi、MAPV同时接种，三针间隔为0、1、5个月。均作免疫前后抗体测定或OT，同时接种组的抗－HBs及MAPV之BA抗体及OT的阳转率分别为100％、92．59％及81．82％－90．0％与单独接种组的96．49％、90．24％和79．25％－87．50％，无显著差异，未见异常反应，一般反应轻微，二组无显著性差异，表明HBV可与BCG、MAPV同时接种。     

Immune response of vaccinated and non-vaccinated mice to Coccidioides posadasii infection

An immunogenic, recombinant protein of the fungal respiratory pathogen, Coccidioides posadasii, was previously identified as a beta-1,3-glucanosyltransferase homolog (Gel1) and shown to confer protection to C57BL/6 mice against coccidioidomycosis. However, little is known about the nature of the humoral and cellular immune responses of these vaccinated mice to intranasal infection with a lethal inoculum of C. posadasii spores compared to non-immune control animals. Our studies showed that protective immunity in mice vaccinated with two 1 microg doses of the recombinant Gel1 (rGel1) plus adjuvant was characterized by high titers of antigen-specific IgG2c and elevated levels of interleukin (IL)-12 and interferon-gamma (IFN-gamma) production at 7-14 days post-challenge compared to significantly lower levels of the respective antibody and cytokines in non-immune, infected mice. Mice immunized with either 0.2 or 5 microg doses of rGel1 plus adjuvant were less well protected and showed evidence of a marked decrease in the level of T helper-type 1 (T(H)1) immune response. Early T(H)1 immune regulation is essential for protection against pulmonary infection with Coccidioides, and the dose of the rGel1 vaccine narrowly defines the nature of immune response in the lungs of infected mice.     

Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice

West Nile virus (WNV) is a mosquito-transmitted flavivirus and an emerging pathogen in many parts of the world. In the elderly and immunosuppressed, infection can progress rapidly to debilitating and sometimes fatal neuroinvasive disease. Currently, no WNV vaccine is approved for use in humans. As there have been several recent outbreaks in the United States and Europe, there is an increasing need for a human WNV vaccine. In this study, we formulated the ectodomain of a recombinant WNV envelope (E) protein with the particulate saponin-based adjuvant Matrix-M™ and studied the antigen-specific immune responses in mice. Animals immunized with Matrix-M™ formulated E protein developed higher serum IgG1 and IgG2a and neutralizing antibody titers at antigen doses ranging from 0.5 to 10 μg compared to those immunized with 3 or 10 μg of E alone, E adjuvanted with 1% Alum, or with the inactivated virion veterinary vaccine, Duvaxyn^® WNV. This phenotype was accompanied by strong cellular recall responses as splenocytes from mice immunized with Matrix-M™ formulated vaccine produced high levels of Th1 and Th2 cytokines. Addition of Matrix-M™ prolonged the duration of the immune response, as elevated humoral and cellular responses were maintained for more than 200 days. Importantly, mice vaccinated with Matrix-M™ formulated E protein were protected from lethal challenge with both lineage 1 and 2 WNV strains. In summary, Matrix-M™ adjuvanted E protein elicited potent and durable immune responses that prevented lethal WNV infection, and thus is a promising vaccine candidate for humans.     

Characterization of a multi-epitope peptide with selective MHC-binding capabilities encapsulated in PLGA nanoparticles as a novel vaccine candidate against Toxoplasma gondii infection

No effective human vaccine against Toxoplasma gondii (T. gondii) has yet been developed; however, a protective vaccine using immunogenic peptides in a safe delivery vehicle system offers promise. Here, we employed bioinformatics to design a multimeric recombinant T. gondii vaccine using predicted T and B cell epitopes of SAG1, AMA1, ROP2, and GRA4 proteins based on their binding capabilities to common major histocompatibility complex (MHC) molecules. Furthermore, we encapsulated the expressed protein in poly lactic-co-glycolic acid (PLGA) nanoparticles as a delivery vehicle and also used alum as an adjuvant to determine the vaccine potency of this multimeric antigen. BALB/c mice were vaccinated and then challenged with T. gondii RH strain, and the survival rate and cytokine profiles were studied. Mice vaccinated with the multi-epitope-based vaccine, both with and without PLGA, had greater Th1 immune responses, survival rates, specific antibody titers, and IFN-γ and IL-2 levels than controls, while the alum-adsorbed vaccine stimulated a Th2-type humoral immune response.     

Superior immunogenicity of HCV envelope glycoproteins when adjuvanted with cyclic-di-AMP,a STING activator or archaeosomes

Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers. To further improve neutralizing antibody responses in recipients along with robust T cell responses, we have explored the immunogenicity of different adjuvants when formulated with the HCV rE1E2 vaccine in mice.Our data show that cyclic di-adenosine monophosphate (c-di-AMP) and archaeosomes elicit strong neutralizing antibodies similar to those elicited using aluminum hydroxide/monophosphoryl lipid A (Alum/monophos. /MPLA) and MF59. However, both c-di-AMP and archaeosomes induced a more robust cellular immune response, which was confirmed by the detection of vaccine-specific poly-functional CD4⁺ T cells. We conclude that these adjuvants may substantially boost the immunogenicity of our E1E2 vaccine. In addition, our data also indicates that use of a partial or exclusive intranasal immunization regimen may also be feasible using c-di-AMP as adjuvant.     

Baculovirus as an avian influenza vaccine vector: differential immune responses elicited by different vector forms

Baculovirus is an enveloped virus that infects insects in nature and has emerged as a novel vaccine vector. We previously constructed a recombinant baculovirus displaying the hemagglutinin protein (HA) of avian influenza virus (AIV) on the viral envelope (Bac-HA64), and demonstrated the induction of humoral responses in immunized mice. To improve the vector design and explore how the vector forms influence the vaccine efficacy, we constructed two more baculoviruses Bac-CHA and Bac-CHA/HA64. Bac-CHA expressed HA after transducing the host cells while Bac-CHA/HA64 not only expressed HA but also displayed HA on the envelope. After administration into BALB/c mice, all three vectors elicited HA-specific humoral (IgG1, IgG2a and hemagglutination inhibition titers), mucosal (IgA titers) and cellular (interferon (IFN)-γ and IL-4 producing T cells and IFN-γ(+)/CD8(+) T cells) immune responses. Intriguingly, the magnitudes and types of responses hinged on the vaccine form and administration route. Via intranasal (i.n.) and subcutaneous (s.c.) inoculation, the HA-displaying vectors Bac-HA64 and Bac-CHA/HA64 triggered stronger humoral and mucosal responses than Bac-CHA, but upon intramuscular (i.m.) injection the HA-expressing vectors (Bac-CHA and Bac-CHA/2HA64) elicited more robust humoral and cellular responses than Bac-HA64. Via either administration route, the dual form vaccine Bac-CHA/HA64 gave rise to superior or at least comparable HA-specific immune responses than the other two vaccine forms, implicating the potential of Bac-CHA/HA64 as a vaccine candidate against AIV infection.     

Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Abeta antibody response with Alum to Quil A adjuvant switch

Beta-amyloid (Abeta) peptide has been proposed to be a causal factor in Alzheimer's disease (AD). Currently being investigated, active and passive Abeta-immunotherapy significantly reduce Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brains of APP transgenic (APP/Tg) mice. Immunization with Abeta42 formulated in the Th1-type adjuvant QS21 was beneficial for AD patients with significant titers of anti-Abeta antibodies, however, 6% of participants developed meningoencephalitis, likely due to anti-Abeta-specific autoimmune Th1 cells. Thus, successful Abeta vaccination requires the development of strong antibody responses without Th1-type cellular immunity. In this study, we compared the induction of humoral immune responses with Th1-type (Quil A) and Th2-type (Alum) adjuvants singly and in combination, using our novel epitope vaccine composed of self B cell epitope Abeta(1-15) and foreign T cell epitope PADRE (PADRE-Abeta(1-15)-MAP). Formulated in Quil A, this vaccine resulted in significantly higher anti-Abeta antibody responses in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, compared with Alum. Anti-Abeta antibodies induced by Alum were predominantly IgG1 type accompanied by lower levels of IgG2a and IgG2b. Quil A induced robust and almost equal titers of anti-Abeta antibodies of IgG1 and IgG2a isotypes and slightly lower levels of IgG2b. Switching adjuvants from Alum to Quil A induced higher concentrations of antibodies than injections with Alum only, however slightly lower than Quil A only. Switching both adjuvants did not change the profile of antibody responses generated by the initial adjuvant injected. These results suggest that switching from Alum to Quil A would be beneficial for AD patients because anti-Abeta antibody production was enhanced without changing the initially generated and likely beneficial Th2-type humoral response.     

Influenza antigen-sparing by immune stimulation with Gram-positive enhancer matrix (GEM) particles

Gram-positive enhancer matrix (GEM) particles, produced from non-genetically modified Lactococcus lactis bacteria have an inherent immunostimulatory activity. It was investigated whether co-administration of GEM particles can reduce the amount of influenza subunit vaccine (HA) necessary to protect mice from viral infection. Decreasing HA amounts of 5, 1, 0.2 and 0.04μg admixed with GEM particles were tested in intramuscular immunizations. Combinations of GEM and seasonal HA (A/Wisconsin/67/2005 [H3N2]) induced significantly higher systemic and better Th1/Th2-type balanced immune responses than HA alone. Addition of GEM to 0.04μg HA resulted in similar HI titers as 1-5μg non-adjuvanted HA. To test the protective efficacy of the adjuvanted combination, mice were immunized with influenza subunit vaccine A/PR/8/34 (H1N1) and then challenged with live virus (A/PR/8/34). Mice immunized with 1μg HA+GEM showed undetectable virus titers in the lungs 5 days after challenge, whereas mice immunized with 1μg HA alone showed detectable levels of virus in the lungs. Interestingly, mice vaccinated with the 0.04μg HA+GEM vaccine demonstrated reduced lung virus titers and a reduction in weight that was similar as that in mice vaccinated with 1μg non-adjuvanted HA. These results indicate that the use of GEM as immunostimulant allows for a strong reduction in the antigen dose as compared to the benchmark vaccine by using GEM particles. Thus, addition of GEM can strongly potentiate immunogenicity of influenza subunit vaccine both quantitatively and qualitatively.     

Intramuscular immunization with a vesicular stomatitis virus recombinant expressing the influenza hemagglutinin provides post-exposure protection against lethal influenza challenge

Vaccines currently licensed for the prevention of seasonal influenza induce antibodies against the influenza hemagglutinin (HA) and neuraminidase (NA) contained in the vaccine preparation but require at least 2 weeks after immunization for the development of protective immunity. These vaccines do not induce protective responses quickly enough to blunt the effects of infection when administered after exposure. We have developed a novel vaccine based on recombinant vesicular stomatitis virus which expresses the influenza hemagglutinin (rVSV HA) and protects mice from lethal influenza challenge when the vaccine is administered intramuscularly at least 24 h after delivery of the influenza challenge virus. To our knowledge this is the first vaccine that effectively protects animals from lethal influenza challenge when delivered by a systemic route after influenza exposure has occurred. The induction of HA-specific immune responses by the vaccine is necessary for full protection from challenge, because animals immunized with an empty rVSV vector were not protected equally. Our results are consistent with a model in which vaccination induces an immediate antiviral cytokine response, followed by development of humoral and cellular immune responses which act to reduce pulmonary viral loads and accelerate recovery. Consistent with this model, mice vaccinated with the specific vaccine rVSV HA had high levels of IFN-α in the serum by 24 h after challenge/vaccination, developed serum neutralizing Ab to influenza 2 days prior to control animals, and had detectable anti-HA CD8 T cells present in the peripheral blood 3 days prior to control mice.