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EDITORIAL
Year : 2011  |  Volume : 1  |  Issue : 1  |  Page : 3-4  

H1N1 2009 influenza pandemic: Looking for a blessing in disguise


1 Editor in Chief, Department of Pharmacology, Adesh Institute of Medical Sciences and Research, Bathinda - 151 109, India
2 Section Editor, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, USA

Date of Web Publication9-Jun-2011

Correspondence Address:
Rajiv Mahajan
Department of Pharmacology, Adesh Institute of Medical Sciences and Research, Bathinda - 151 109
India
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DOI: 10.4103/2229-516X.81971

PMID: 23776763

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How to cite this article:
Mahajan R, Grover A. H1N1 2009 influenza pandemic: Looking for a blessing in disguise. Int J App Basic Med Res 2011;1:3-4

How to cite this URL:
Mahajan R, Grover A. H1N1 2009 influenza pandemic: Looking for a blessing in disguise. Int J App Basic Med Res [serial online] 2011 [cited 2014 Dec 19];1:3-4. Available from: http://www.ijabmr.org/text.asp?2011/1/1/3/81971

In 2009, the first pandemic of influenza of the present century was reported, with its widespread ramifications. The last update released by World Health Organization (WHO) on August 6, 2010 reported the spread of laboratory-confirmed cases of pandemic influenza H1N1 2009 in more than 214 countries, including more than 18,449 deaths. [1] As WHO announced H1N1 influenza to be in postpandemic phase on August 10, 2010, it is expected that H1N1 2009 virus will circulate as seasonal influenza virus for some years to come and localized outbreaks of various magnitude can occur. [2]

As the threat of localized outbreaks of H1N1 influenza looms large, continuous surveillance is demanded. Such vigilance is especially critical in the immediate postpandemic period, when the behavior of the H1N1 virus as a seasonal virus cannot be reliably predicted. WHO recommended activities during the postpandemic period included-advice on epidemiological and virological monitoring, vaccination, and the clinical management of cases. On the WHO chart, vaccination remains important as a means of reducing the morbidity and mortality caused by influenza viruses, and it strongly recommends vaccination of high-risk individuals in countries where influenza vaccines are available. [2]

Influenza vaccines and drugs work by targeting two surface-proteins of the influenza A virus, namely, hemagglutinin (HA) and neuraminidase (NA). The problem with vaccine development is the presence of different subtypes of HA and NA proteins. There are 16 known HA subtypes and nine known NA subtypes. [3] So, many different combinations of HA and NA proteins are possible, such as H1N1, H2N2, H3N2, H5N1, to name a few. Thus, the development of a universal flu vaccine effective against all strains of influenza A proves challenging. Another hindrance to the development of a universal vaccine for influenza A is its capacity to undergo mutations. It is the most frequent influenza virus capable of acquiring variations, by progressive antigenic drifts and occasional antigenic shifts. [4] Thus, the vaccine developed against a particular strain may subsequently become ineffective against it due to development of variations.

To overcome these problems, trivalent vaccine is in use since 1945. Released every year, the vaccines contain three virus strains that are expected to affect the United States in the upcoming winter. Due to the change in the types of influenza viruses circulating each year, some of the virus components of the influenza vaccines are changed every year. The trivalent vaccine recommended by WHO and US Food and Drug Administration to be used during 2010-2011 season will consist of the influenza virus strains A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2), and B/Brisbane/60/2008. The A/California/7/2009 (H1N1) virus is the same pandemic strain that was used in the 2009 H1N1 monovalent vaccine. As sporadic influenza A (H3N2) activity continues to be reported in several countries, H3N2 component is a part of the trivalent vaccine. [5]

But this trivalent vaccine, developed as an answer to tackle the problem of antigenic shift and combating circulating strains of influenza A has its own share of problems. Every year, a new vaccine has to be released. Moreover, if a pandemic is reported after the release of the vaccine, it is not possible to incorporate the pandemic strain in the vaccine on war-footing. Precisely because of the same reason, monovalent H1N1 vaccine was developed during the 2009 pandemic. The presently recommended trivalent vaccine for 2010-2011 season is not available across the globe. Above all, as the immunity conferred by the vaccine is not long lasting, it is obligatory to be immunized again in anticipation of the next influenza season. These inbuilt tribulations of influenza vaccinations have always fascinated scientists to look for a universal influenza shot-a single influenza vaccine effectual against many influenza strains. Till recently, the idea was assumed to be speculative, but now it seems that there is light at the end of the tunnel!

In a joint effort, scientists at the Emory University, University of Chicago, and Columbia University have recognized that patients infected with the first wave of H1N1 2009 (infected before H1N1 vaccine was produced) and subsequently recovered, had an extraordinary immune response. They have isolated neutralizing antibodies from nine such patients, and majority of the neutralizing antibodies induced by infection were broadly cross-reactive with all recent annual H1N1 strains, as well as the highly pathogenic 1918 H1N1 and avian H5N1 strains. [6]

Starting the study with an aim of isolating antibodies from recovered patients as a therapy for infected patients, scientists isolated a significant number of pandemic H1N1-reactive plasmablasts from the blood of the infected patients and amplified the heavy and light chain variable region genes of the sorted cell using single-cell polymerase chain reaction. These genes were cloned and expressed as monoclonal antibodies, and the antibodies were screened for reactivity by enzyme-linked immunosorbent assay. Of the 86 antibodies generated in this fashion, 46 antibodies were reactive to pandemic H1N1 and 15 antibodies were specifically reactive to HA. Eleven of the 15-HA-specific antibodies were able to neutralize the virus in vitro and were labeled as neutralizing antibodies. Of these 11 neutralizing antibodies, five were found to bind with high affinity to most H1 strains, including all from the vaccines of the past 10 years, the 1918 pandemic strain, and to the H5 of a highly pathogenic avian influenza strain (H5N1). Interestingly, these five neutralizing antibodies bounded specifically to conserved epitopes in the HA stalk region (stem-reactive antibodies). Thus, half of the neutralizing (5/11) and 10% (5/46) of all antibodies induced by pandemic H1N1 infection bounded to a conserved, critical epitope on the HA stalk. When tested in vivo, these antibodies potently protected and rescued mice from lethal challenge with pandemic H1N1 or antigenically distinct influenza strains. [6]

It has already been proved by two independent studies that the stalk region of HA mutate much less and is refractory to neutralization escape; and antibodies specific against this region have already been advocated to be promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses. [7],[8] The same team, after isolating stem-reactive antibodies, is working with an unnamed biotechnology company to develop an influenza vaccine, based on this concept. Another team at the National Institute of Health is testing a 2-step vaccine that uses DNA from stem-reactive antibodies to prime the immune system, followed by regular influenza vaccination. A study showed that this 2-step approach protected mice against influenza strains from 1934 through 2007; and the vaccine is now in human-trial phase. [9] In the light of this knowledge, it can be predicted safely that stem-reactive antibodies are thus promising as therapeutic agents against pandemic H1N1, as well as most other H1N1 and H5N1 influenza strains, and have all the potential to be developed into a universal influenza vaccine.

 
   References Top

1.World Health Organization. Global Alert and Response (GAR)-Pandemic (H1N1) 2009-update 112: Weekly update [Last updated 2010 Aug 06]. Available from: http://www.who.int/entity/csr/don/2010_08_06/en/index.html. [Last cited on 2011 Feb 07].  Back to cited text no. 1
    
2.World Health Organization. Global Alert and Response (GAR)-WHO recommendations on the post-pandemic period [Last updated on 2010 Sep 10]. Available from: http://www.who.int/csr/disease/swineflu/notes/briefing_20100810/en/index.html . [Last cited on 2011 Feb 07].  Back to cited text no. 2
    
3.Goel MK, Goel M, Khanna P, Mittal K. Pandemic influenza A (H1N1) 2009 vaccine: An update. Indian J Med Microbiol 2011;29:13-8.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.Lio OT, Poon LL. One step closer to universal influenza epitopes. Expert Rev Anti Infect Ther 2009;7:687-90.  Back to cited text no. 4
    
5.Virology blog. Trivalent influenza vaccine for the 2010-2011 season [Last updated on 2010 Mar 10]. Available from: http://www.virology.ws/2010/03/10/trivalent-influenza-vaccine-for-the-2010-2011-season/# [Last cited on 2011 Feb 08].  Back to cited text no. 5
    
6.Wrammert J, Koutsonanos D, Li G, Edupuganti S, Sui J, Morrisey M, et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 2011;208:181-93.  Back to cited text no. 6
    
7.Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, et al. Antibody recognition of a highly conserved influenza virus epitope. Science 2009;324:246-51.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  
8.Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 2009;16:265-73.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Swine flu survivors developed super flu antibodies. Express Pharma 2011;6:32.  Back to cited text no. 9
    



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