GlaxoSmithKline (GSK) has shed some light on the H1N1 vaccine production arena, announcing that they have received orders from governments aiming to stockpile a new candidate H1N1 vaccine. The announcement provides several data points on plans for the vaccine.
GSK expects the first doses of the vaccine to be available 4-6 months after receiving the virus seed from the WHO. I think the virus seed could be ready as early as June, putting vaccine availability in the Q4 2009 timeframe. They have noted that they plan to complete the 2009/2010 seasonal influenza vaccine campaign by the end of July. This is consistent with the proposed timeline for H1N1 vaccine production, allowing it to begin in August.
Of course all of this is subject to regulatory approval. However the pandemic vaccine will be produced by a similar process to the seasonal vaccine and in the same facilities, so it seems improbable that there would be any significant regulatory delays. GSK already received a European license for a pandemic vaccine based on a ‘mock-up’ dossier, and expects this to facilitate a faster registration of the new A (H1N1) vaccine. This is currently being discussed with EU regulatory authorities.
A notable aspect of the GSK pandemic vaccine is the proposed inclusion of GSK’s proprietary ASO3 adjuvant. ASO3 is an alpha-tocopherol based oil-in-water emulsion, similar to Novartis’s MF59. Adjuvants typically stimulate immune responses to the antigen components of the vaccine, and can generate a higher immune response with lower amounts of antigen when compared to the unadjuvanted formulation. This effect can decrease the amount of antigen required in a dose and hence increase the number of vaccine doses that can be produced. In addition an adjuvanted flu vaccine has the potential to provide protection even if the strain drifts, a distinct possibility with the current H1N1.
This is of such interest because, to the best of my knowledge, no non-alum adjuvanted vaccine has been approved by the US FDA. A recent NIAID/NIH sponsored workshop was held to discuss adjuvants, including their inclusion in pandemic flu vaccines. The emergence of H1N1 could accelerate the resolution of the adjuvant debate as the US Department of Health & Human Services grapples with the potential public health emergency.
The seasonal influenza vaccine contains a 15mcg dose of each of three antigens, and no adjuvant. If prepared as a pandemic vaccine, the H1N1 vaccine will contain only the single antigen. It is unknown at this time how much unadjuvanted antigen will have to be included in the vaccine formulation to elicit seroprotection, but for the H5N1 vaccine as much as 90mcg per dose has been required. The adjuvanted dose could be as low as 3-10mcg, realising a significant increase in the available doses. The H5N1 pandemic vaccine requires two doses to seroprotect, so it is also possible that the H1N1 vaccine will be similar, requiring 2 doses. This will place additional strain on the available manufacturing capacity. An adjuvant may become mandatory for translating the available manufacturing capacity into sufficient doses to meet global demand, and GSK clearly intend on travelling down that pathway. It will be fascinating to see how FDA reacts.
