Pandemic influenza vaccines

At its meeting on 3-4 December 2009, the Global Advisory Committee on Vaccine Safety (GACVS) preliminarily reviewed the safety of pandemic A (HlNl) influenza vaccines [29 ]. From 21 September to 2 December 2009, tens of millions of doses of the 2009 HlNl vaccine were administered, providing the basis for this first safety review by the GACVS. Pandemic influenza vaccines include live attenuated vaccines, inactivated unadjuvanted vaccines (split, subunit virion, or whole virion), and inactivated adjuvanted vaccines (split or subunit virion). At the time of the GACVS review, it was estimated that nearly 150 million doses of vaccine had been distributed in many countries around the world. About 30% of those 150 million doses were adjuvanted vaccines. 

An observational study looked at the response of inflammatory bowel disease (IBD) patients to the 2009 HlNl pandemic influenza vaccine. Although the vaccine was well tolerated, overall seroprotection was only 50%, and on subanalysis those patients who were immunosuppressed had a seroprotection level of only 44% compared with 64%... 

Two studies looked at whether using the adjuvanted HlNl pandemic influenza vaccine (Pandemrix ) overcame the issue of a reduced antibody response for renal transplant patients. The first study showed that although the adjuvanted vaccine provided a slight improvement in seroprotection, it remained significantly less than even the nonadjuvanted vaccine in healthy controls [44 ]. The other study showed that despite a booster dose, seroprotection levels after the adjuvanted vaccine remained poor [45 ]. Of note, the authors commented that 6 out of 107 vaccinated renal transplant patients developed new donor-HLA antibodies following vaccination. This phenomenon has not been commented on in the other recently published studies of renal transplant patients following vaccination with the HlNl vaccine. 

Candela S, PergoHzzi S, Ragni P, Cavuto S, NobiUo L, Di Mario S, et aL An early (3-6 weeks) active surveillance study to assess the safety of pandemic influenza vaccine Focetria in a province of Emflia-Romagna region, Italy - Part One. Vaccine 2013 31(10) 1431-7. 

Aikawa N, Campos L, Goldenstein-Schainberg C, Saad C, Ribeiro A, Bueno C, et al. Effective seroconversion and safety following the pandemic influenza vaccination (anti-HlNl) inpatients with juvenile idiopathic arthritis. Scand J Rheumatol 2013 42(l) 34-40. 

Current recommendations for the use of influenza vaccine in adults are based on a single injection. This may not be valid in case of a new pandemic caused by an antigenic shift of the influenza virus. Currently, the only group for whom a second dose is recommended comprises children who have never been immunized. However, when two-dose regimens in adults have been studied, the second dose of vaccine has not been associated with higher rates of reactions than the first. People who have a stronger local reaction after a first injection are more likely to have another such reaction after a second injection (31). 

Children in the United States are vaccinated against a growing list of diseases pertussis (whooping cough), diphtheria, tetanus, measles, mumps, rubella, varicella (chicken pox), polio, hepatitis B, and pneumococcal disease. Annual influenza vaccination, depending on the prevalent viral strain, is recommended for most age groups. The HlNl influenza pandemic of 2009 saw the rapid development of an effective vaccine however, a vaccine for HIV remains ellusive. 

Influenza and HIV provide particular challenges. The potential virulence of influenza was demonstrated during the 1918 worldwide pandemic in which an estimated 50 million people died. Any influenza vaccine that would provide protection against multiple strains would have to address the problem of both genetic drift and genetic shift. The inability to... 

Aerosol and nasal delivery of vaccines and antiviral drugs against seasonal and pandemic influenza. Expert Review of Respiratory Medicine, 4,... 

Global Advisory Committee on Vaccine Safety (GACVS). Safety of pandemic A (HlNl) influenza vaccines. Wkly Epidemiol Rec 2010 85 29-31,3-4 December 2009. 

When the pandemic influenza HlNl vaccines were authorised for use during the 2009/2010 flu season, there was only limited data on safety and immunogenicity available. Over the past years, an extensive amount of safety and efficacy data from postmarketing surveillance studies has been published. 

Following the WHO declaration of an influenza pandemic in 2009, countries quickly worked to manufacture their own vaccines based on the WHO-prepared strains and reagents. During this pandemic, three vaccines were approved for use in Europe - Celvapan , Focetria and Pandemrix . Since 2009, there have been a number of observational studies looking at them. 

Pregnant women were disproportionately affected by the HlNl pandemic and had a higher risk for serious complications from the infection. Multiple studies during the 2009 HlNl influenza pandemic support the safety of either the adjuvanted [39 ] or nonadjuvanted influenza vaccine [40 J in pregnant women. Although these studies are small and so cannot pick up on rare outcomes, the findings are consistent. 

Wijnans L, Lecomte C, de Vries C, Weibel D, Sammon C, Hviid A, et al. The incidence of narcolepsy in Europe before, during, and after the influenza A(HlNl)pdm09 pandemic and vaccination campaigns. Vaccine 2013 31(8) 1246-54. 

Miller E, Andrews N, SteHitano L, Stowe J, Winstone AM, Shneerson J, et al. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/HINI2009 influenza vaccine retrospective analysis. BMJ 2013 346. 

Azevedo LS, Gerhard J, Miraglia JL, Precioso AR, Tavares Timenetsky MdS, Agena F, et al. Seroconversion of 2009 pandemic influenza A (HlNl) vaccination in kidney transplant patients and the influence of different risk factors. Transpl Infect Dis 2013 15(6) 612-8. 

Cordero E, AydiUo TA, Perez-Ordonez A, Torre-Cisneros J, Lara R, Segiua C, et al. Deficient long-term response to pandemic vaccine results in an insufficient antibody response to seasonal influenza vaccination in solid organ transplant recipients. Transplantation 2012 93(8) 847-54. 

ViUa D, Gubbay J, Sutherland DR, Laister R, McGeer A, Cooper C, et al. Evaluation of 2009 pandemic HlNl influenza vaccination in adults with lymphoid malignancies receiving chemotherapy or following autologous stem ceU transplant. Leuk Lymphoma 2013 54(7) 1387-95. 

New human H5N1 influenza vaccines are available, although further research is still required to investigate their effectiveness. Vaccination could be used to protect high-risk populations and to try to contain emergence of a potential pandemic. Available data do not go beyond 16 months for vaccine protection. Currently formulated H5N1 vaccines require at least two doses to be administered, 21 days apart, in order to provide reliable rates of sero-response. 

The development of sialidase-based inhibitors as anti-influenza drugs has provided a first line-of-defence to safeguard humanity against a potential pandemic and most importantly to buy time for vaccine and further anti-influenza drug development. Most exciting is that new opportunities exist for next generation sialidase inhibitor development. 

---