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Indian Journal of Medical Microbiology, Vol. 29, No. 1, January-March, 2011, pp. 13-18 Review Article Pandemic influenza A (H1N1) 2009 vaccine: An update MK Goel1, M Goel2, P Khanna1, K Mittal3 1 Department of Community Medicine, Pt. B.D. Sharma, PGIMS, Rohtak, India Correspondence Address: M K Goel, Department of Community Medicine, Pt. B.D. Sharma, PGIMS, Rohtak, India, drmanishgoel2000@yahoo.co.in Date of Submission: 27-Nov-2010 Code Number: mb11004 PMID: 21304188 DOI: 10.4103/0255-0857.76517 Abstract The world witnessed a the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the World War I. The past experiences with influenza viruses and this pandemic of H1N1 place a considerable strain on health services and resulted in serious illnesses and a large number of deaths. Developing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that vaccination is the most effective ways to mitigate the negative effects of the pandemic. The vaccines for H1N1 virus have been used in over 40 countries and administered to over 200 million people helped in a great way and on August 10, 2010, World Health Organization (WHO) announced H1N1 to be in postpandemic period. But based on knowledge about past pandemics, the H1N1 (2009) virus is expected to continue to circulate as a seasonal virus and may undergo some agenic-variation. As WHO strongly recommends vaccination, vigilance for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses along with safety surveillance of the vaccines is necessary. This review has been done to take a stock of the currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period.Keywords: Influenza A (H1N1), H1N1 vaccines, postpandemic, pandemic, India The world witnessed a novel influenza virus (H1N1) in early 2009 from Mexico [1] which was declared as pandemic by World Health Organization (WHO), on June 11, 2009. [2] This was the first influenza pandemic in this century and fourth overall since first flu pandemic was reported during the world war I. [3] Since June 2009, the H1N1 pandemic has spread to almost all countries. [4] The past experiences with influenza viruses and this pandemic of H1N1 place a consider-able strain on health services and resulted in serious illnesses and a large number of deaths. The young people, pregnant women and those with chronic diseases seem to have the highest rate of complications. Develop-ing countries were declared more likely to be at risk from the pandemic effects, as they faced the dual problem of highly vulnerable populations and limited resources to respond H1N1. The public health experts agreed that one of the most effective ways to control H1N1 pandemic is by vaccinating at-risk populations. [5] The immediate efforts to develop vaccine against H1N1 started at the global level. This review has been done to disseminate the information regarding the H1N1 situation and also to take an account of currently available H1N1 vaccines and their possible use as public health intervention in the postpandemic period. To access relevant and the latest information regarding situations updates and recommendations, the data sources of WHO and its related agencies, different news agencies drug controller authorities and Ministry of Health of different countries, and different regulatory authorities for monitoring and implementation of vaccine standards, adverse effects following vaccination (AEFI) and postmarketing surveillance (PMS) data was searched. Information from different vaccine manufacturers through their data bases, via email and personal communication was also obtained. For detailed information regarding vaccine trials (methodology, efficacy, safety, etc.) articles was searched in databases like Medline and Cochrane library. The Vaccine Development The vaccine for H1N1 pandemic was produced by Novartis AG in Switzerland. In fact, the level of preparation was so rapid that by the time WHO declared the H1N1influenza a pandemic, the first batch of the vaccine was produced on the next day. [6] Later on, a few more vaccines have been developed and as on Aug 2010, more than 30 different vaccines were available in three different formulations of - Adjuvant monovalent influenza A (H1N1) 2009 vaccine (with alum or MF-59), [7] non-adjuvant monovalent influenza A (H1N1) 2009 vaccine [8] and as live attenuated influenza vaccine (LAIV) against influenza A (H1N1) 2009. [9] Efficacy Several clinical trials needed to establish safety, efficacy and adverse effect profile of the presently available vaccines had been conducted and many are in process. Findings of some of the important trials are shown in [Table - 1]. The bridging studies in India and other places also found the vaccine to be efficacious. [13],[14] Two previous studies on seasonal vaccines also support that non-adjuvant influenza vaccine may be immunogenic at a lower dose. [15],[16] Safety Some common solicited local and systemic adverse events had been noted and more so in the case of adjuvant vaccines. [7],[8] These are local i.e., pain, erythema, ecchymosis, induration, swelling and systemic adverse events viz., headache, myalgia , malaise, fatigue, sore throat, chills, nausea, arthralgia, sweating, cough, wheezing, chest tightness and other difficulties in breathing. Association of any other serious adverse effects and death had not been noticed in any of the vaccine trials. [7],[8] Several systems have been set up for monitoring the safety of influenza and other vaccines and to report any clinically significant AEFI. The Committee for Medicinal Products for Human Use (CHMP) has recommended to specifically report on ′Adverse events of special interest′ i.e., neuritis, convulsions, anaphylaxis, encephalitis, vasculitis, Guillain-Barré syndrome, Bell′s palsy, demyelinating disorders and laboratory-confirmed vaccination failure. [19] Uppsala Monitoring Centre and Vaccine Adverse Event Reporting System (VAERS) are some of such system which are collecting the available information which can support monitoring vaccine safety and analysis of AEFI and PMS data. [20],[21] H1N1 Vaccines and India The WHO reported that worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18,449 deaths. [4] In India, till date more than 1500 deaths are reported due to H1N1 swine flu and low levels of pandemic influenza virus continued to circulate in western India. [22] Moreover in India influenza outbreaks are also observed in rainy season. The national government had taken note of the account and the Government of India decided to purchase 1.5 million doses of non-adjuvanted pandemic influenza (H1N1) vaccine and approved the usage after successful completion of a bridging study among 100 subjects in Delhi and Pune to determine the vaccine′s behaviour among Indians. [14] The government has vaccinated frontline health workers with this vaccine across the country. [23] In other major scientific advancement, India on 4 th of June 2010 unveiled its first-ever indigenous vaccine against H1N1 influenza virus, created by Zydus Cadilla from an H1N1 strain given by WHO the single-shot vaccine called Vaxiflu-S. [24] This is an inactivated (whole virion) monovalent (H1N1) 2009 influenza vaccine. The vaccine is recommended for individuals aged 18 years and above and should be administered as a single 0.5-mL intramuscular injection preferably in the region of the deltoid muscle of the upper arm. Three other Indian companies are also ready with their indigenous swine flu vaccines. Pune-based Serum Institute of India (SII) has developed an H1N1 vaccine, Nasovac, in the form of a nasal spray, and is available for usage across the country from 15 th July 2010. [25] However, it is not recommended for pregnant women and lactating mothers. Other companies i.e., Bharat Biotech (Hyderabad) and Panacea (Delhi) will also be out with their versions in coming days. [24] One another company, Biological E Ltd., plans to develop a genetically engineered vaccine with technology and licensing from the US firm VaxInnate Corporation. [25] Who should be Vaccinated? In contemplating equal access to influenza vaccines, three key issues are of utmost importance: manufacturing capacity, cost incurred and the delivery of the vaccine.[26] The doses of the vaccine which could be produced with the existing capacity is very large but it would not be nearly enough for every needy in the world. This gap could be met by reducing number of doses. Additional studies regarding similar or other vaccines in various age groups with different dosage schedules but with standardized agents, methodologies must be undertaken. The data thus obtained should be properly analyzed to make timely recommendations. The WHO recommended that the priority for the vaccination should be given to the following groups.[27]
Other considerations: [28] It has been proposed that inactivated 2009 H1N1 vaccine can be administered at the same visit as any other vaccine, including pneumococcal polysaccharide vaccine. The live 2009 H1N1 vaccine can be administered at the same visit as any other live or inactivated vaccine EXCEPT seasonal LAIV. If both types of LAIV are inadvertently administered during the same visit or at an interval less than 4 weeks, neither vaccine needs to be repeated. If more than one vaccine is being administered on the same day, these should be administered in different anatomical sites if possible. Moreover, the live H1N1 and live seasonal should not be administered on the same day and should be, separated by at least 28 days. Simultaneous administration is not expected to be harmful to the patient, but the immune response might be suboptimal for one or both of the vaccines. However, the live H1N1 and inactivated seasonal flu vaccines can be administered simultaneously or at any interval between doses. The inactivated H1N1 and live seasonal can be administered simultaneously or at any interval between doses. All persons in a recommended vaccination target group who had a flu-like illness but did not have a laboratory test indicating 2009 H1N1 virus infection should receive the 2009 H1N1 vaccine. It should be noted that the vaccine trials conducted with the vaccines have some limitations. The studies were conducted during a time, when the pandemic virus was circulating. Responses could be somewhat different, if vaccines trials were conducted under different epidemiological circumstances. The immunogenicity data are difficult to extrapolate to pregnant females or to adults who have underlying immune suppression or high-risk conditions, for which influenza vaccine is also necessary. We can only speculate on this basis of experience with traditional seasonal vaccines, that the immune responses in older children, pregnant women and immuno-competent adults with chronic conditions are roughly similar to those of healthy non-pregnant adults. [29],[30] Moreover, the entire safety with the vaccines cannot be ascertained in smaller studies, conducted for vaccine efficacy. For this we need to conduct bigger studies. There existed several situations in which the vaccines which were earlier recommended safe and effective for the usage had been withdrawn for some reason or the other.[31],[32],[33] Several lacunae are still there in the minds of people regarding H1N1 vaccination. Many of them fear of side effects. Moreover majority of vaccines only provides immunity for 8-12 months so many health professionals consider taking it futile. On August 10, 2010, though WHO announced H1N1 to be in postpandemic period yet, knowledge about past pandemics, it is expected that influenza virus will continue to circulate for some years. The vaccination remains important means of reducing the morbidity and mortality. WHO strongly recommends vaccination of high-risk individuals. [34] Influenza A virus infects humans, swine, birds, poultry and horses and other animals and divided into subtypes on the basis of two surface proteins: hemagglutinin (HA) and neuraminidase (NA). There are 16 known HA subtypes and nine known NA subtypes. Many different combinations of HA and NA proteins are possible e.g., H1N1, H2N2, H3N2, H5N1, etc. As shown by the past experiences [Table - 2], it is the most frequent influenza virus capable of agenic variations in response to infection or vaccination, by progressive antigenic drifts or agenic shifts (via genetic reassortment occurring among different species) and is responsible for pandemics.[35] Moreover its behaviour cannot be reliably predicted in the presence of other influenza A viruses (i.e., H1N1, H5N1 and H3N2) which are also circulating among humans. This concern was recognized as early as 1947; leading to establishment of the WHO Global Influenza Surveillance Network (GISN). [36] GISN over the last 10 years had recommended 14 changes in different influenza vaccine strains. So, in these situations vigilance on the part of national health authorities remains important for regular updating of the composition of influenza vaccines, based on an assessment of the future impact of circulating viruses i.e., not only the antigenic and genetic characteristics of the viruses but also their prevalence, geographic distribution, rate of spread along with safety surveillance of the vaccines. Conclusions The vaccines for H1N1 virus have been produced and are available in limited quantities for those people that are most at risk. These include health care workers and specific priority groups. Vaccines can prevent you from getting ill. Since the beginning of September 2009, pandemic vaccines have been used in over 40 coun-tries and administered to over 200 million people. The countries using the H1N1 vaccines have been monitoring the vaccines and found out that the vaccines safety is similar to seasonal flu vaccines. [5] Based on the information we have now, [4],[5] the advantages of getting vaccinated, if the vaccine is available, appear to far outweigh the risks. Acknowledgement We are thankful to Dr. Chanderkant Laharia, for his help in providing the important information and access to some of the important links without which this update would not be possible. References
Copyright 2011 - Indian Journal of Medical Microbiology The following images related to this document are available:Photo images[mb11004t2.jpg] [mb11004t1.jpg] |
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