Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial

Objective Seasonal vaccination has been consistently shown to significantly reduce morbidity and mortality because of influenza epidemics, even in healthy, working adults. Here we report the results of the yearly licensing studies of the past 11 influenza seasons (1997–2007) with a trivalent, inactivated whole virus vaccine with an aluminum phosphate adjuvant system. Methods Sixty healthy volunteers per age group (18–60 years and 60 years and older) were enrolled to receive vaccination each year, thus, a total of 1080 subjects were studied. Serum antibody titers were measured by hemagglutination inhibition (HI). Results: The vaccine met the criteria for licensing each year, meaning seroprotection (achievement of an HI titer of >1:40 in >70% of subjects); seroconversion, i.e. a >4‐fold increase in HI antibody titer, or reaching a titer of >1:40, in >40% of subjects; and an increase in geometric mean titers by >2·5‐fold. Side effects were rare and mild. The same method was used to produce a pre‐pandemic vaccine against influenza A (H5N1), which has been shown to be safe and immunogenic in humans. Conclusions We conclude that the method presented is safe, effective and may serve as a useful approach to seasonal and pandemic vaccine production even in less well‐developed countries by means of technological transfer.

Section: Discussionmentioning

confidence: 99%

Yearly licensing studies from 1997 to 2007 of the inactivated whole virus seasonal influenza vaccine fluval – a useful approach to pandemic vaccine development even in less well developed countries?

Vajó¹,

Kosa²,

Szilvasy

et al. 2008

“…One study showed that two vaccinations with 90 μg HA of a non‐adjuvanted vaccine induced an antibody response at protective levels in only half of an immunologically naive population 23 . Another study found that two 30 μg doses of an aluminium‐adjuvanted split‐virion H5N1 vaccine were needed to induce an immune response that met two of three criteria required for European Union licensure 24 . As the amount of antigen tested in both these studies is substantially more than is needed for protection against seasonal influenza strains, and given current limits on worldwide vaccine production capacity, measures to increase the immune response and reduce the antigen content are essential.…”

Section: Introductionmentioning

confidence: 99%

“…As the amount of antigen tested in both these studies is substantially more than is needed for protection against seasonal influenza strains, and given current limits on worldwide vaccine production capacity, measures to increase the immune response and reduce the antigen content are essential. This is particularly important as clinical trials have shown that two doses of adjuvanted H5N1 vaccine are necessary to satisfy regulatory criteria for immunogenicity 24 , 25 , 26 . Use of improved adjuvants may provide the best approach for cross‐reactive immune responses for both seasonal and pre‐pandemic vaccination.…”

Section: Introductionmentioning

confidence: 99%

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Banzhoff

Pellegrini

Giudice

et al. 2008

Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.

“…Many promising H5N1 vaccines including whole‐virion, split‐virion, adjuvanted and non‐adjuvanted vaccines have been developed and clinically evaluated, 6 , 11 , 12 , 13 some of which have been granted production licensure in different regions. All these achievements arm us with a powerful, if not sufficient, defence against the next human influenza pandemic.…”

Section: Problem and Prospectmentioning

confidence: 99%

Safety and immunogenicity of Sinovac’s prototype pandemic influenza H5N1 vaccines: a review on clinical trials

Qiu

Yin

2008

Sinovac Biotech started to develop prototype pandemic influenza H5N1 vaccines in March 2004. On 2 April 2008, Sinovac’s inactivated, aluminium‐adjuvanted, whole‐virion prototype pandemic influenza A (H5N1) vaccine (PanFlu™) was granted production licensure by the China regulatory authority State Food and Drug Administration. The whole‐virion H5N1 vaccine was manufactured in embryonated hens’ eggs using the reassortant strain NIBRG‐14 (A/Vietnam/1194/2004‐A/PR/8/34) as vaccine virus. It showed good safety, immunogenicity and cross‐reactivity in immunologically naïve adults. In primed adults, the vaccine induced a strong booster response. Plasma from a vaccinated individual showed a beneficial effect following passive immunotherapy of an H5N1 human infection case. This article reviews the process, status and results of clinical evaluation of Sinovac’s whole‐ and split‐virion H5N1 vaccines by focusing on the whole‐virion vaccine.