A one-year study of trivalent influenza vaccines in primed and unprimed volunteers: immunogenicity, clinical reactions and protection

Three hundred volunteers were divided into two age groups, 14-30 years and 31-60 years. Each participant was immunized intramuscularly with a subunit, whole virus or absorbed whole virus vaccine, containing A/Bangkok/1/79 (H3N2), A/Brazil/11/78 (H1N1) and B/Singapore/222/79 influenza virus. Serum haemagglutination-inhibition (HI) antibody response, protection, and reactogenicity were studied after one and two doses of the vaccines. Primary immunization induced much higher percentages of HI antibody titres greater than or equal to 100 against all three vaccine viruses and much higher geometric mean titres (GMT) in volunteers with pre-immunization titres greater than or equal to 18 as compared to those with pre-immunization titres less than 18. Secondary immunization did not result in an increase of GMTs or antibody titres greater than or equal to 100 in volunteers with pre-immunization titres less than 18. On the whole, the response to the subunit vaccine was similar to that to the other two vaccines. To influenza B/Singapore/222/79 virus the response was lowest after administration of the whole virus vaccine in the age group 31-60 years. Over 50% of the HI titres greater than or equal to 100 found after immunization in the different vaccine and age groups were still present after one year. Serologically established infections during the winter months following immunization amounted to 15% in the subunit vaccine group, 6% in the whole virus vaccine group, and 10% in the adsorbed whole virus vaccine group. Local and systemic reactions to all three vaccines were mild in nature. Local reactions after primary immunization were much less frequent following administration of the subunit vaccine as compared to the other two vaccines, especially in the younger age group. In comparison to primary immunization, after booster immunization the incidence of local reactions was higher for the subunit vaccine and lower for the adsorbed whole virus vaccine. In the age group 14-30 years the incidence of local reactions after primary as well as booster immunization was much greater in females than in males, especially when the adsorbed whole virus vaccine was used.     

Safety and immunogenicity of seasonal trivalent inactivated influenza vaccines in pregnant women

BackgroundIn the United States, seasonal inactivated influenza vaccine (IIV) is recommended for pregnant women; however, in early 2009, immunization rates were low, partly due to limited prospective data and concerns about vaccine safety.ObjectiveWe conducted a randomized study of two licensed seasonal trivalent IIVs (IIV3) to assess their safety and immunogenicity in pregnant women.Study DesignIn this prospective, randomized clinical study, 100 pregnant women, 18–39 years of age and ≥14 weeks gestation received a single intramuscular dose of 2008–2009 Fluzone® or Fluarix®. Injection site and systemic reactions were recorded for 7 days after vaccination and serious adverse events (SAEs) and pregnancy outcomes were documented. Serum samples collected before and 28 days after vaccination were tested for hemagglutination inhibition (HAI) antibody levels.ResultsThe majority of the injection site and systemic reactions were mild and self-limited after both vaccines. No fever ≥100 °F was reported. There were no vaccine-associated SAEs. Immune responses to influenza vaccine antigens were similar for the two study vaccines, with robust HAI responses against influenza A strains, and relatively lower responses for influenza B strains.ConclusionSeasonal inactivated influenza vaccines were well tolerated and immunogenic in pregnant women.

• ClinicalTrials.gov identifier NCT00905125.

Synopsis: In this prospective clinical trial, we demonstrated that immunization with seasonal trivalent, inactivated influenza vaccine in the second and third trimester of pregnancy is immunogenic and safe.     

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults

Purpose

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009–2010 TIV) or a Yamagata B-lineage strain (2008–2009 TIV).

Methods

Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009–2010 TIV, 2008–2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination.

Results

One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009–2010 and 2008–2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT_QIV/GMT_TIV > 0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups.

Conclusion

QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages.     

Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: A Phase I dose escalating study in healthy volunteers

Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney – cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18–50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1 × 10⁵, 1 × 10⁶, or 1 × 10⁷ tissue culture infectious dose 50% (TCID₅₀) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008–2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose–response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants further development.     

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)₃. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.     

Provider knowledge of trivalent inactivated and high-dose influenza vaccines

Objective

The objective of this study was to assess provider knowledge about trivalent inactivated and high dose influenza vaccines. Hence, a 20-item survey was distributed to providers within the Internal Medicine department at an urban academic medical center.

Results

Two hundred and eighty-one (24.5%) providers responded. The correct response rate was 63.2%. The highest performing subspecialties were infectious diseases (80.5%), endocrinology (69.2%), and pulmonary (68%). Those who received an influenza vaccine during the most recent season scored significantly higher than those who did not (63.6% vs. 43.6%, p = .001). Areas where respondents did poorly included questions pertaining to contraindications to immunizations (27.4%), common adverse events after immunization (29.2%), target antigen (73.5%), number of strains in the trivalent inactivated vaccine (62.9%), and time to immunity (61.4%). High dose vaccine knowledge was poor, with 37% of providers unaware of its existence.

Conclusion

Significant gaps in provider knowledge exist regarding both trivalent inactivated and high dose influenza vaccines.     

Responses of volunteers to inactivated influenza virus vaccines.

Three different types of bivalent influenza virus vaccine, a whole virus, an aqueous-surface-antigen vaccine and an adsorbed-surface-antigen vaccine were tested at three dosage levels in volunteers primed with respect to only one of the haemagglutinin antigens present in the vaccines. The local and systemic reactions to all three vaccine types were mild in nature and, following first immunization, the aqueous-surface-antigen vaccine was the least reactogenic. The serum haemagglutination-inhibiting antibody response to the A/Victoria/75 component of the vaccines to which the volunteer population was primed, was greatest following immunization with the aqueous-surface-antigen vaccine; the greatest antibody response to the A/New Jersey/76 component of the vaccines was observed following immunization with whole virus vaccine.     

Systemic,nasal and oral live vaccines against Pseudomonas aeruginosa: A clinical trial of immunogenicity in lower airways of human volunteers

Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies. We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination. All vaccines were based on a recombinant fusion protein of the highly conserved P. aeruginosa outer membrane proteins OprF and OprI as antigen. While systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was noted only after nasal and oral vaccinations. We conclude that nasal and oral OprF-OprI vaccines are promising candidates for development of antipseudomonal immunisation through inducing a specific antibody response in the lung.     

Antigenicity and immunogenicity of equine influenza vaccines containing a Carbomer adjuvant.

Equine influenza vaccines containing inactivated whole virus and Carbomer adjuvant stimulated higher levels and longer lasting antibody to haemagglutinin in ponies than vaccines of equivalent antigenic content containing aluminium phosphate adjuvants. Five months after the third dose of vaccine containing Carbomer adjuvant, ponies were protected against clinical disease induced by an aerosol of virulent influenza virus (A/equine/Newmarket/79, H3N8). In contrast ponies which received vaccine containing aluminium phosphate adjuvant were susceptible to infection and disease. There was an inverse correlation between prechallenge levels of antibody detected by single radial haemolysis (SRH) and duration of virus excretion, pyrexia and coughing. All ponies with antibody levels equivalent to SRH zones of > or = 154 mm2 were protected against infection and all those with levels > or = 85 mm2 were protected from disease.     

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n = 52), lineage drift (n = 15) and lineage mismatch (n = 43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.     

Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring

In preparation for pandemic vaccine safety monitoring, we assessed adverse events reported to the Vaccine Adverse Event Reporting System following receipt of trivalent inactivated influenza vaccines among adults from 1990 through 2005. We calculated reporting rates for nonserious, serious, and neurological adverse events. We reviewed reports of recurrent events and deaths, as well as reports identified through advanced signal detection. The most frequently reported events were local reactions and systemic symptoms. Guillain-Barré syndrome was the most frequently reported serious event (0.70 reports per million vaccinations). Adverse event reporting rates have been reasonably constant over time. No new safety concerns emerged after our review of 15 years of post-licensure surveillance data. These findings provide useful information if pandemic vaccine is rapidly distributed and pre-licensure data are limited.     

Adverse reactions of trivalent influenza vaccine in HIV-infected individuals

In this study, we assessed the adverse reactions to influenza vaccination in HIV-infected individuals. From November 2006 to January 2007, a total of 203 HIV-infected persons were recruited. Demographic data were collected. Subjects were evaluated 48 h and 15 days after vaccination for symptoms and significant health events as possible side effects. Participants were instructed to measure their temperature in the morning and evening for 2 days post-immunization and to assess injection site and systemic adverse reactions. 80.3% of the subjects were male. The mean age of the subjects was 36.9 +/- 7.9 years. Local and systemic reactions were reported by 61 (30%) and 62 (30.5%) persons, respectively. The most common adverse reactions to the influenza vaccine included skin redness (37 cases), induration (32 cases), and pain (55 cases) as local reactions, and fever (22 cases), myalgia (46 cases), headache (12 cases) and weakness (35 cases) as general reactions. 1.4 % of the subjects had fever over 38.5 degrees C. There were significant associations between myalgia and flushing with CD4 counts (P<0.05). We found no relationship between adverse reactions and sex, history of smoking, allergy, alcohol, and drug usage, stage of HIV infection, anti-retroviral therapies, anti-TB medication and previous vaccination. We concluded that inactivated influenza vaccine administered in HIV-infected adults did not result in potential adverse events in this study population.     

A study of the immunogenicity of smallpox vaccines

The authors report on a series of tests to determine the immunogenic properties of smallpox vaccines of varying degrees of infectivity. Rabbits were immunized with serial dilutions of the vaccines and challenged twenty days later with intradermal neurovaccine or testicular vaccine, with injection of testicular vaccine into the testes, or with intracerebral neurovaccine. It was possible to demonstrate a correlation between the infectivity of the immunizing vaccine and the degree of immunity conferred, as shown by the serum antibody level and by the reaction to the challenge inoculation. It also appears that the immunogenicity of the vaccines is determined not only by the number of active virus particles they contain but also by their virulence, the more virulent giving greater immunity in smaller doses. Unduly virulent vaccines, however, may give rise in humans to severe and painful reactions.     

国产流感病毒裂解疫苗的免疫原性及安全性效果评价

目的观察国产流感病毒裂解疫苗的免疫原性及安全性。方法通过对疫苗接种者的随访调查和血清学检测,分析国产疫苗和进口疫苗间的免疫差异,从而对国产疫苗进行效果评价。结果接种国产疫苗和进口疫苗后,除个别有发热现象外,未发现其他异常反应,且两组的发热比率经检验差异无统计学意义;国产疫苗H1N1亚型、H3N2亚型和B型HI抗体阳转率、GMT增长倍数以及易感人群下降率,与进口疫苗相比差异均无统计学意义。结论国产疫苗具有很好的安全性和免疫原性。     

A graded-dose study of inactivated, surface antigen influenza B vaccine in volunteers: reactogenicity, antibody response and protection to challenge virus infection.

One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 micrograms of HA or saline alone in a 0.5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response. The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 micrograms HA and least for those given 5 micrograms HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 micrograms HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of greater than 40 following immunization: for volunteers given 5 micrograms HA the g.m.t. increased from 16.6 to 86.1; and for those given 10 and 20 micrograms HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20.     

Adjuvanted inactivated influenza A(H3N2) vaccines induce stronger immunogenicity in mice and confer higher protection in ferrets than unadjuvanted inactivated vaccines

Influenza viruses are major respiratory pathogens and the development of improved vaccines to prevent these infections is of high priority. Here, we evaluated split inactivated A(H3N2) vaccines (A/Uruguay/716/2007) combined or not with adjuvants (AS03, AS25 and Protollin) and administered by three different routes, intramuscular (i.m.), intranasal (i.n.) or intradermal (i.d.), both in BALB/c mice and in ferrets. Ferrets were challenged with the homologous strain A/Uruguay/716/2007 (H3N2) or the heterologous strain A/Perth/16/2009 (H3N2) 4 weeks after the second immunization with A/Uruguay/716/2007 vaccines. Temperature, weight loss and clinical signs were monitored on a daily basis and nasal washes were performed to evaluate viral titers in the upper respiratory tract. All adjuvanted vaccines induced stronger humoral immune responses than unadjuvanted ones in both mice and ferrets. In mice, the AS03- and AS25-adjuvanted i.m. vaccines generated a mixed Th1–Th2 response at 6 and 19 weeks after the last immunization as shown by the production of IgG1 and IgG2a antibodies as well as the production of IL-2, IL-4 and IFN-γ by CD4+ and CD8+ T cells. HAI and MN titers were also higher in those groups when compared to the i.n. Protollin-adjuvanted and unadjuvanted groups. The Protollin-adjuvanted i.n. vaccine induced a more Th1 oriented response with a significant production of IgA in bronchoalveolar lavages. In ferrets, the AS03- and AS25-adjuvanted i.m. vaccines also induced higher HAI and MN titers compared to the other groups. These vaccines also significantly decreased viral titers after challenge with both the homologous A/Uruguay/716/2007 (H3N2) and the heterologous A/Perth/16/2009 (H3N2) strains. In conclusion, adjuvanted influenza vaccines elicited stronger humoral response in mice and conferred greater protection in naive ferrets than unadjuvanted ones. Interestingly, the AS25 adjuvant system containing monophosphoryl-lipid-A appears particularly promising for developing more potent inactivated influenza vaccines.     

Immunogenicity of trivalent subunit and split influenza vaccines (1989-90 winter season) in volunteers of different groups of age

Trivalent split or subunit influenza vaccines [A/Shangai/11/87 (H3N2), A/Singapore/6/86 (H1N1) and B/Yamagata/16/88] recommended for the 1989-90 winter season and licensed in Italy, were administered to 149 volunteers of three different age groups (elderly, middle-aged and young). Antibody production was determined in pre- and postvaccination sera by haemagglutinin inhibition test and the results were evaluated as protection and response rates. The split vaccine was more immunogenic than the subunit preparation, especially against the B virus strain. Age had no obvious impact on the degree of responsiveness to vaccination.     

Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children.

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19-50 years), children (3-12 years) and the elderly (> or =65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.     

Key points in evaluating immunogenicity of pandemic influenza vaccines: A lesson from immunogenicity studies of influenza A(H1N1)pdm09 vaccine

IntroductionImmunogenicity studies on pandemic influenza vaccine are necessary to inform rapid development and implementation of a vaccine during a pandemic. Thus, strategies for immunogenicity assessment are required.ObjectiveTo identify essential factors to consider when evaluating the immunogenicity of pandemic influenza vaccines using the experience in Japan with the influenza A(H1N1)pdm09 vaccine.MethodsWe conducted a search of observational studies using PubMed and IchushiWeb. Search terms included “influenza vaccine AND (immunogenicity OR immune response) AND Japan AND (2009 OR pdm09) NOT review,” and was limited to studies conducted in humans.ResultsA total of 33 articles were identified, of which 16 articles met the inclusion criteria. Immunogenicity of the commercially available influenza A(H1N1)pdm09 vaccine satisfied the international criteria for influenza vaccine immunogenicity in all study populations. The most remarkable immune response was observed in junior high school students, while the lowest immune response was observed in hematological malignancy patients. Similar to immunogenicity studies on seasonal influenza vaccines, factors such as patient background (e.g., age, underlying condition, pre-vaccination titer, body mass index, etc.) and study procedure (e.g., concurrent measurement of pre- and post-vaccination antibody titer, effects of infection during the study period) may have affected the assessment of immunogenicity to the influenza A(H1N1)pdm09 vaccine. In addition, prior vaccination with the seasonal influenza vaccine may inhibit antibody induction by the influenza A(H1N1)pdm09 vaccine.ConclusionsThis review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics.     

Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans

The increasing number and density of the human population, the emergence of lethal influenza strains, and the potential use of designer influenza virus as a bioweapon, collectively highlight a critical need for more rapid production of influenza vaccines and less invasive means of delivery. We have developed a nonreplicative adenovirus-vectored influenza vaccine that can be produced without the prerequisite of growing influenza virus. This new class of vaccines can be administered as a nasal spray or skin patch by personnel without medical training. We report here that adenovirus-vectored nasal and epicutaneous influenza vaccines were well tolerated by human volunteers. The nasal vaccine was more potent than its epicutaneous counterpart under the adjuvant-free experimental condition. These results provide the foundation for further human testing of needleless vectored vaccines as promising alternatives to current vaccines.