Journal of Immunology and Clinical Research

Universal Influenza Vaccines - A Short Review

Review Article | Open Access

  • 1. Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, USA
+ Show More - Show Less
Corresponding Authors
Bao-Zhong Wang, Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30322, USA

Since the development of the first vaccine against influenza virus in 1940s, considerable progress has been made in preventing this devastating disease. Despite of the encouraging advances, influenza vaccine research and development still remain challenging mainly due to the hurdle of antigenic drift and shift of viral immunogens. The current seasonal influenza vaccines need to be reformulated annually and provide only limited protection in the case of mismatch. The reoccurrence of seasonal epidemics and occasional outbreak of pandemics have urged the development of novel influenza vaccines capable of eliciting broad cross-protective immune responses. In this scenario, antigens composed of conserved regions shared among various influenza subtypes have raised great hopes for such vaccines. Delicate antigen design and integrated molecular adjuvants in combination with improved delivery and controlled release strategies present the promising directions towards universal influenza vaccine development. The present review summarizes the recent progress in such endeavors. Influenza matrix protein 2 and stalk domain of the hemagglutinin draw general interests for improved antigen design. Additionally, epitopes that are recognized by cytotoxic T lymphocytes (CTLs) become attractive targets for antigen design. On the other hand, multiple delivery platforms including virus-like particles, microneedles and nanoclusters could be employed to facilitate the optimization of an affordable universal influenza vaccine.


•    Broad cross-protection
•    Immunity
•    Influenza
•    Vaccine


Wang L, Zhang H, Compans RW, Wang BZ (2013) Universal Influenza Vaccines - A Short Review. J Immunol Clin Res 1: 1003.


Influenza virus is one of the most important respiratory pathogens with significant medical and economic burdens [1-3]. It belongs to genera A, B and C of the family Orthomyxoviridae with type A viruses being the primary pathogens claimed for seasonal and pandemic influenza outbreaks [4]. Type A viruses can be further divided into different subtypes based on the serotypes of their main surface antigens hemagglutinin (HA) and neuraminidase (NA) [5]. So far, 17 HA and 9 NA subtypes have been identified. Phylogenetically, 16 HA subtypes are categorized into two groups (H1, H2, H5, H6, H8, H9, H11, H12, H13 as well as H16 in group 1, and H3, H4, H7, H10, H14 as well as H15 in group 2) [6]. Historically, H1 (H1N1), H2 (H2N2) and H3 (H3N2) have caused influenza pandemics in humans and resulted in millions of death [7]. At present, H1N1 and H3N2 viruses are causing epidemic infections in humans and constitute the main components of seasonal influenza vaccines. However, the efficacy of current influenza vaccine is limited due to the antigenic drift. Further, the occasional antigenic shift of HA and NA may cause the emergence of new influenza pandemics. In addition, non-human influenza viruses may acquire the capacity for transmission in humans as well [8]. With the frequent infection by highly pathogenic avian influenza A (HPAI) H5N1 in humans in recent years, and the most recent human infection by a novel avian influenza virus (H7N9) in China [9,10], this concern has become more urgent. Although current influenza vaccines are effective in battling closely matched viruses, the major hurdles are the need to produce new vaccines every season, the uncertainty in choice of the correct strains, and the inability to prevent a new influenza pandemic. Improved vaccines inducing broadly protective immune responses against multiple type A influenza viruses, namely universal influenza vaccines, are needed, not only for seasonal but also for pandemic influenza prevention. Conserved epitopes are potential immunogens for such vaccines [11,12]. Combined strategies including improved design of antigens, integrated molecular adjuvants, new antigen delivery techniques and vaccination regimens should be considered together to overcome current obstacles in the development of a universal influenza vaccine [6,13-17].


Several approaches have been improved to induce broad cross-protection based on current vaccine strategies. Coadministration of adjuvants is a classic but effective approach. Typically influenza vaccines do not induce CD8+ cytotoxic T lymphocyte (CTL) responses which are required to control viral pathogens. By using adjuvants, co-administrated vaccines are able to induce CTL responses that target highly conserved epitopes among different viruses. Therefore, co-administrated adjuvant presents a potential approach for inducing broad crossprotection. Several mechanisms may be involved in adjuvantinduced T cell responses [18-20]. Some adjuvants, such as alum and emulsions, can trap antigens at the injection site and increase recruitment and activation of antigen presenting cells (APCs) [21]. The others are essential ligands for pattern recognition receptors (PRR) such as Toll-like receptors (TLRs), and are highly effective in inducing potent adaptive immune response [22]. For instance, the TLR-5 ligand flagellin has been modified into different forms to enhance influenza immunity for broad protection [17,23-26]. This protein can be expressed in a membrane-anchored form and be incorporated into influenza virus-like particles (VLPs) which have been reported to confer heterosubtypic protection [23,24]. In a fusion protein form with the conserved extracellular domain of the influenza matrix protein 2 (M2e), flagellin was shown to induce high levels of M2e-specific antibodies and confer complete protection against a heterologous viral challenge [17]. In addition to adjuvants, several newly developed vaccine delivery platforms have been employed to enhance the immune response and crossprotection. Of them, VLPs are one of the most striking platforms [27-29]. By mimicking the organization and conformation of native viruses but lacking the replicative genomic information, VLPs can be produced in heterologous expression systems on large scales, thus can be safer and cheaper vaccine candidates [30,31]. Because of the self-assembly feature of VLPs, targeted viral antigens form multimeric complexes displaying a high density of epitopes. The size and conformation of these particles are similar to intact native virions [24,32-35] . Moreover, VLPs can enter both MHC class I and class II antigen processing pathways in APCs, eliciting both humoral and cellular immune responses [35-37].With the development of nanotechnology, microneedles and nanoparticles have been used as new platforms for influenza vaccine delivery for enhanced immune protection. Inactivated virus, VLPs and subunit vaccines were coated on microneedles and induced improved protective immunity by skin vaccination [38-40]. Co-immunization with A/Puerto Rico/8/1934 (A/ PR8, H1N1) HA DNA vaccines and inactivated virus by coating on a microneedle patch conferred immune protection against lethal A/PR8 and pandemic 2009 H1N1 challenge in mice [15]. Being assembled into nano size with controlled antigen release, nanoparticles exhibit adjuvant effects and stimulate APCs upon binding and/or internalization [41-43], and have been employed to deliver influenza vaccine for enhanced immune protection [44- 46]. However, in many cases the amount of antigen loaded into the nanoparticle is low due to the presence of polymer core, and the process by which the particle is made can damage or unfold the antigen [41]. Newly developed nanoparticles bring the hope to overcome these limitations. For instance, novel nanoclusters assembled directly from influenza HA and/or M2e with no need of encapsulating agent was shown to maximize antigenic protein load. The gentle fabrication conditions allow the antigen to maintain their native form. These nanoclusters were found to induce broadly cross-protection (Wang et. al, unpublished data). Recently, self-assembling influenza nanoparticle vaccines have also been established by fusing viral HA to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides [47,48]. This self-assembling nanoparticle vaccine elicited neutralizing antibodies to two highly conserved vulnerable HA structures that are targets of universal vaccines: the stem and the receptor binding site on the head [49,50]. Resulting antibodies neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. Self-assembling nanoparticles improve the potency and breadth of influenza immunity and indicate a potential platform for development of universal influenza vaccines.


The influenza genome is composed of eight segments which encode 11 viral proteins including the major surface glycoproteins HA and NA [51,52]. These viral proteins endow targets for influenza vaccines that induce protection against similar viruses [53]. Influenza matrix protein 2 (M2) is an integral transmembrane protein. Although only a few copies are expressed on the surface of influenza A virions, relatively dense presentation of this protein was found on the surfaces of infected host cells [54]. This protein consists of 97 amino acids, including 24 amino acid residues at the N-terminus which form the ectodomain of M2 (M2e) [55]. M2 exists as a homotetramer formed by two disulfide-linked dimers which assemble into an ion channel, and plays an important role in uncoating the virus during viral entry [56-58]. Since M2e is highly conserved among influenza A viruses, it has been considered as a promising target for inducing cross protection against different influenza A viruse subtypes [59,60]. Studies have shown that M2e-specific antibodies can reduce the plaque size [61,62]. Passive immunization with these antibodies reduced virus titers in the lungs of mice infected with influenza A viruses [63,64]. However, M2e specific antibodies can rarely be induced by a natural influenza infection or seasonal vaccination [65,66]. Several groups attempted to overcome the low immunogenicity of M2e using various platforms such as fusing M2e protein with carrier molecules including keyhole limpet hemocyanin (KLH), hepatitis B virus core (HBc), multiple antigenic peptides (MAP) or fusing four repeats of M2e to a membrane anchor from influenza virus HA [17,67-69]. In all these studies, M2e-specific immune responses were induced but the protective effect to different virus was weak. Partial protection or severe sickness was observed in virus challenge experiments with immunized laboratory animals. One possible reason is that minor variation of M2e sequences from different viruses still exists although this protein is considered to be relative conserved, which may contribute to the different protective efficacy of M2e vaccines against various viral challenge [70]. One approach to overcome this limitation is to integrate multiple M2e repeats from different viruses into one vaccine platform. A membrane-anchored form of M2e fusion protein containing multiple M2e sequences has been incorporated into VLPs and induced M2e-specific antibodies reactive to different influenza viruses, conferring improved cross-protection against various subtypes of influenza virus including A/California/2009 (H1N1) or A/Philippines/82 (H3N2) [16]. Another reason for the weak protection of M2e vaccine candidates investigated in the past is that most of these M2e were presented in a non tetrameric form [71-73], or without an appropriate vaccine delivery platform even though a tetrameric M2e was employed [74]. In a recent study, structure-stabilized M2e tetramers were expressed and purified from a baculovirus-derived insect cell protein expression system, and were assembled into highly immunogenic nanoclusters. The resultant nanoclusters induced high level of M2e-specific humoral and cellular immune response, conferring complete protection against lethal challenges with either A/California/2009 (H1N1) or A/Philippines/82 (H3N2) virus (Wang et. al, unpublished data). The progress in coming up with enhanced antigen design, integrated adjuvants, novel delivery and controlled release strategies (such as VLPs, microneedles or nanoclusters) suggest that M2e has great potential for development of broadly protective influenza A virus vaccines.


The HA protein plays pivotal roles in influenza virology and is highly immuogesnic [75,76]. This envelop glycoprotein is anchored to the virus membrane as spikes consisting of two subunits, HA1 and HA2, up on the cleavage of the immature protein HA0 [77-79]. The architecture of HA can be dissected into the membrane-distal head (contains the most majority of HA1) and membrane-proximal stalk (comprises the N- and C-terminal portion of HA1 and the complete HA2) [80,81]. The HA1 head mediates binding of virion to host cell receptor and is essential for attachment of virus to target cells while HA2 promotes the fusion between viral and host endosomal membrane and virus entry [76]. HA2 contains a 23 amino acid long fusion peptide in its N-terminus followed by two α helices, A-helix and CD-helix [49,82,83]. At neutral pH, the fusion peptide is buried inside of the molecule. After the virus is taken up into endosome where HA is exposed to low pH, these motifs undergo dramatic conformational rearrangements which trigger the extrusion of the fusion peptide from interior of the molecule to the near end of the endosomal membrane [84,85]. Conventional neutralizing antibodies against HA are known to bind to host receptor binding domain within HA1 that are subjected to antigenic drift and are highly variable among different subtypes, which helps to explain the restricted protection of these antibodies against specific virus subtypes [86,87]. In comparison, the sequence of HA stalk is highly conserved across all influenza subtypes, which provides this domain the potential as a conserved epitope candidate for universal influenza vaccine design [12,88]. This rationale is further supported by the recent achievement in discovering several broadly neutralizing antibodies specifically against the HA stalk domain [49,50,89-91]. The identification of CR6261, a broadly neutralizing antibody against most group 1 influenza virus (including H1, H5, H9 and some H2 subtypes), has revealed the presence of a conserved epitope located in the A-helix of HA2 [49]. Meanwhile, a newly discovered monoclonal antibody CR8020 with broad neutralizing activity exclusively against group 2 HAs has been shown to protect mice against the lethal dose challenge of H3N2 as well as H7N7 [91]. The epitope against CR8020 consists of the C-terminal portion of the fusion peptide and surrounding residues. By screening large number of human peripheral blood plasma cells, Davide Corti and colleagues isolated monoclonal antibodies that recognized the HA of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses [89]. It is suggested that these antibodies recognize the fusion peptide as well as A-helix of HA stalk domain which are the regions bound by CR8020 and CR6261, respectively [90,91]. Taken together, these studies provide valuable information for potential cross-protective epitopes that researchers can consider to work with. To fulfill the ultimate goal of obtaining a universal influenza vaccine that can elicit broad-cross immunity, efforts have been made to optimize the way that epitopes are presented to the host immune system. Various approaches have been employed including the generation of virus like particles (VLPs), nano-grade particles, and recombinant carrier proteins. In an attempt to produce a HA-stalk-oriented immunogen for broad cross immunity, a truncated HA that lacks the global head (residues 52-277 of HA1) from A/Puerto Rico/8/1934 (PR8, H1N1 subtype) was created and could be stably incorporated into VLPs when co-transfected with HIV Gag-based construct in mammalian cells. The resultant VLP vaccine elicited antibodies that were cross-reactive among group 1 HA subtypes and provided protection against lethal homologous challenge although some weight loss was observed in mice [6]. It was proposed that this headless HA is in its neutral-pH conformation which resembles what it looks like in the native form of full length HA such that the elicited antibodies may exert their neutralizing function by inhibiting the transition of HA2 from neutral pH to low pH conformation and further inhibiting the fusion process. There are other studies suggesting the soluble HA2 in the absence of HA1 actually exists in the low-pH conformation, which may not be favorable for eliciting antibodies that are neutralizing [92]. In order to obtain soluble stalk domain that is in native state (neutral-pH conformation), Gayathri Bommakanti and other researchers designed a novel stalk construct (in the context of A/Hong Kong/1968, HK68, H3N2) containing 1-172 aa of HA2 connected to the portions of HA1 (both its N– and C-terminal regions) that constitute part of the stalk domain [93]. By using protein design and minimization methods, the parts of HA1 that interact with HA2 were included in the designed molecule and two hydrophobic residues in HA2 were mutated to charged residues in order to destabilize the low-pH conformation. This stalk construct was expressed in Escherichia. coli (E. coli) system and refolded from inclusion body to its neutral-pH conformation. This highly immunogenic construct exhibited binding ability to a previously identified broad neutralizing antibody 12D1 and protected mice from lethal homologous challenge. This research provides us an example for delicate antigen design based on careful structural and biophysical analyses. As described above, the emerging nanoparticle approach opens another promising avenue for production of multivalent antigen to boost the host immune response. Potential self-assembled nanoparticles as highly effective platform for vaccine design can be a powerful candidate for universal influenza vaccine when combined with the possible cross protective nature of HA stalk domains. Linear epitopes in the form of relatively short peptides in HA can be genetically coupled to certain protein carrier that may function as adjuvant for better vaccine efficacy. One recent example of such approach showed its competence in conferring broad protection against influenza subtypes from both group 1 and group 2 [94]. In this study, the epitope consisting of amino acid 76-130 of HA2 from H3 subtype (HK68), the binding target for neutralizing antibody 12D1, was coupled to the keyhole limpet hemocyanin (KLH) for enhanced antigenicity. This conjugate vaccine elicited antisera reactive to a board range of HAs from H1, H2, H3, H5 and H7 subtypes. It also protected mice from lethal challenge of not only H3, but also H5 and H1 subtypes. It is intriguing to find that the full length HA2, as compared to this conjugate containing only a small fraction of HA2, exhibited actually weaker antigenicity as it induced antisera reactive only to subtypes limited to group 2 influenza viruses. This may imply that inclusion of only the linear epitope by itself may help to elicit a more focused anti-stalk domain response, which is in line with the high protein sequence conservation of this region among both group 1 and group 2 influenza viruses. Another promising carrier protein is bacterial flagellin protein. In the context of fusion protein design, the central variable region of flagellin could be substituted by desired antigen, such as the global head of HA, without affecting its TLR-5 binding activity [95]. This recombinant fusion protein strategy has also proven to be successful in inducing anti-influenza immunity [96,97]. However, so far not much work has been reported for flagellin being used in stalk domain-based vaccine design which might be an attractive approach for universal influenza vaccine production.


B-cell mediated humoral antibody immunity against influenza essentially protects the host from virus infection. As mentioned above, the conserved M2e and HA epitopes are in hope to elicit broad neutralization and protection. As another equally critical immune response against influenza virus, the cytotoxic T lymphocytes (CTLs) mediate cellular immunity by recognizing viral peptides presented on virus-infected epithelial cells [98,99]. These immune-responses are essential for inhibiting virus spread and clearance of infected cells. Epitopes that are recognized by CTLs reside on various influenza proteins including viral nucleoprotein (NP), matrix protein M1, RNA polymerase subunits PB1 and PB2 [100]. The value of combined B and T cell conserved epitopes as enhanced vaccine candidate has been recognized for years [101,102]. Recently, a first-in-human trial of a novel vaccine containing conserved linear epitopes from HA, NP and M1 proteins of both influenza type A and B strains has been carried out [103]. It was found that this vaccine was capable to induce both humoral and cellular immunity and was potentially cross-strain immunogenic. However, due to the small scale of experiment population and moderate elevation of immune responses in vaccinated group, further studies and evaluation need to be performed.


Universal influenza vaccines, as a concept, have been raised for a long time. There is an urgent need to provide broader, universal protection against a broad spectrum of influenza viruses. A lot of attempts have been made in these years; however, not so much progress has been gained. Recently, with the combination of conserved region of influenza virus such as M2e or HA stalk domains with efficient delivery strategies such as VLPs, microneedles or nanoparticles, the light of a universal vaccine finally shows up at the end of a long dark tunnel.


This study was supported by the National Institute of Allergy and Infectious Diseases under grant number R01AI101047 (BZW). The funder had no role in preparation and submission of the manuscript. The authors have declared that no competing interests exist.


1. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004; 292: 1333-1340.

2. Esposito S, Gasparini R, Bosis S, Marchisio P, Tagliabue C, Tosi S, et al. Clinical and socio-economic impact of influenza and respiratory syncytial virus infection on healthy children and their households. Clin Microbiol Infect. 2005; 11: 933-936.

3. Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary Estimates of Mortality and Years of Life Lost Associated with the 2009 A/H1N1 Pandemic in the US and Comparison with Past Influenza Seasons. PLoS Curr. 2010; 2: RRN1153.

4. Hayashida H, Toh H, Kikuno R, Miyata T. Evolution of influenza virus genes. Mol Biol Evol. 1985; 2: 289-303.

5. Hayashida H, Toh H, Kikuno R, Miyata T. Evolution of influenza virus genes. Mol Biol Evol. 1985; 2: 289-303.

6. No authors listed] A revision of the system of nomenclature for influenza viruses: a WHO memorandum. Bull World Health Organ. 1980; 58: 585-591.

7. Steel J, Lowen AC, Wang TT, Yondola M, Gao Q, Haye K, et al. Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio. 2010; 1.

8. Carrat F, Flahault A. Influenza vaccine: the challenge of antigenic drift. Vaccine. 2007; 25: 6852-6862.

9. Steinhauer DA, Skehel JJ. Genetics of influenza viruses. Annu Rev Genet. 2002; 36: 305-332.

10. Mei L, Song P, Tang Q, Shan K, Tobe RG, Selotlegeng L, et al. Changes in and shortcomings of control strategies, drug stockpiles, and vaccine development during outbreaks of avian influenza A H5N1, H1N1, and H7N9 among humans. Biosci Trends. 2013; 7: 64-76.

11. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013; 368: 1888-1897.

12. Graves PN, Schulman JL, Young JF, Palese P. Preparation of influenza virus subviral particles lacking the HA1 subunit of hemagglutinin: unmasking of cross-reactive HA2 determinants. Virology. 1983; 126: 106-116.

13. Krystal M, Elliott RM, Benz EW Jr, Young JF, Palese P. Evolution of influenza A and B viruses: conservation of structural features in the hemagglutinin genes. Proc Natl Acad Sci U S A. 1982; 79: 4800-4804.

14. Song JM, Wang BZ, Park KM, Van Rooijen N, Quan FS, Kim MC, et al. Influenza virus-like particles containing M2 induce broadly cross protective immunity. PLoS One. 2011; 6: e14538.

15. El Bakkouri K, Descamps F, De Filette M, Smet A, Festjens E, Birkett A, et al. Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol. 2011; 186: 1022-1031.

16. Kim YC, Yoo DG, Compans RW, Kang SM, Prausnitz MR. Crossprotection by co-immunization with influenza hemagglutinin DNA and inactivated virus vaccine using coated microneedles. J Control Release. 2013. 

17. Kim MC, Song JM, O E, Kwon YM, Lee YJ, Compans RW, et al. Viruslike particles containing multiple M2 extracellular domains confer improved cross-protection against various subtypes of influenza virus. Mol Ther. 2013; 21: 485-492.

18. Wang BZ, Gill HS, Kang SM, Wang L, Wang YC, Vassilieva EV, et al. Enhanced influenza virus-like particle vaccines containing the extracellular domain of matrix protein 2 and a Toll-like receptor ligand. Clin Vaccine Immunol. 2012; 19: 1119-1125.

19. Skountzou I, Martin Mdel P, Wang B, Ye L, Koutsonanos D, Weldon W, et al. Salmonella flagellins are potent adjuvants for intranasally administered whole inactivated influenza vaccine. Vaccine. 2010; 28: 4103-4112.

20. Eliasson DG, El Bakkouri K, Schön K, Ramne A, Festjens E, Löwenadler B, et al. CTA1-M2e-DD: a novel mucosal adjuvant targeted influenza vaccine. Vaccine. 2008; 26: 1243-1252.

21. De Filette M, Ramne A, Birkett A, Lycke N, Löwenadler B, Min Jou W, et al. The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection. Vaccine. 2006; 24: 544-551.

22. Leroux-Roels G. Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine. 2010; 28 Suppl 3: C25-36.

23. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006; 124: 783-801.

24. Wang BZ, Xu R, Quan FS, Kang SM, Wang L, Compans RW. Intranasal immunization with influenza VLPs incorporating membraneanchored flagellin induces strong heterosubtypic protection. PLoS One. 2010; 5: e13972.

25. Wang BZ, Quan FS, Kang SM, Bozja J, Skountzou I, Compans RW. Incorporation of membrane-anchored flagellin into influenza viruslike particles enhances the breadth of immune responses. J Virol. 2008; 82: 11813-11823.

26. Chaung HC, Cheng LT, Hung LH, Tsai PC, Skountzou I, Wang B, et al. Salmonella flagellin enhances mucosal immunity of avian influenza vaccine in chickens. Vet Microbiol. 2012; 157: 69-77.

27. Huleatt JW, Nakaar V, Desai P, Huang Y, Hewitt D, Jacobs A, et al. Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine. 2008; 26: 201-14.

28. Schneemann A, Speir JA, Tan GS, Khayat R, Ekiert DC, Matsuoka Y, et al. A virus-like particle that elicits cross-reactive antibodies to the conserved stem of influenza virus hemagglutinin. J Virol. 2012; 86: 11686-11697.

29. Pushko P, Pearce MB, Ahmad A, Tretyakova I, Smith G, Belser JA, et al. Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes. Vaccine. 2011; 29: 5911-5918.

30. Haynes JR, Dokken L, Wiley JA, Cawthon AG, Bigger J, Harmsen AG, et al. Influenza-pseudotyped Gag virus-like particle vaccines provide broad protection against highly pathogenic avian influenza challenge. Vaccine. 2009; 27: 530-541.

31. Kingsman SM, Kingsman AJ. Polyvalent recombinant antigens: a new vaccine strategy. Vaccine. 1988; 6: 304-306.

32. Roldão A, Mellado MC, Castilho LR, Carrondo MJ, Alves PM. Virus-like particles in vaccine development. Expert Rev Vaccines. 2010; 9: 1149- 1176.

33. Buonaguro L, Tornesello ML, Buonaguro FM. Virus-like particles as particulate vaccines. Curr HIV Res. 2010; 8: 299-309.

34. Grgacic EV, Anderson DA. Virus-like particles: passport to immune recognition. Methods. 2006; 40: 60-65.

35. Young KR, McBurney SP, Karkhanis LU, Ross TM. Virus-like particles: designing an effective AIDS vaccine. Methods. 2006; 40: 98-117.

36. Wang BZ, Liu W, Kang SM, Alam M, Huang C, Ye L, et al. Incorporation of high levels of chimeric human immunodeficiency virus envelope glycoproteins into virus-like particles. J Virol. 2007; 81: 10869-10878.

37. Bachmann MF, Lutz MB, Layton GT, Harris SJ, Fehr T, Rescigno M, et al. Dendritic cells process exogenous viral proteins and virus-like particles for class I presentation to CD8+ cytotoxic T lymphocytes. Eur J Immunol. 1996; 26: 2595-2600.

38. Ruedl C, Storni T, Lechner F, Bächi T, Bachmann MF. Crosspresentation of virus-like particles by skin-derived CD8(-) dendritic cells: a dispensable role for TAP. Eur J Immunol. 2002; 32: 818-825.

39. Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR. Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J Control Release. 2010; 142: 187-195.

40. Quan FS, Kim YC, Vunnava A, Yoo DG, Song JM, Prausnitz MR, et al. Intradermal vaccination with influenza virus-like particles by using microneedles induces protection superior to that with intramuscular immunization. J Virol. 2010; 84: 7760-7769.

41. Weldon WC, Martin MP, Zarnitsyn V, Wang B, Koutsonanos D, Skountzou I, et al. Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity. Clin Vaccine Immunol. 2011; 18: 647-654.

42. Cheng X, Liu R, He Y. A simple method for the preparation of monodisperse protein-loaded microspheres with high encapsulation efficiencies. Eur J Pharm Biopharm. 2010; 76: 336-341.

43. Jin T, Zhu J, Wu F, Yuan W, Geng LL, Zhu H. Preparing polymer-based sustained-release systems without exposing proteins to water-oil or water-air interfaces and cross-linking reagents. J Control Release. 2008; 128: 50-59.

44. O’Hagan DT, Valiante NM. Recent advances in the discovery and delivery of vaccine adjuvants. Nat Rev Drug Discov. 2003; 2: 727-735.

45. Galloway AL, Murphy A, DeSimone JM, Di J, Herrmann JP, Hunter ME, et al. Development of a nanoparticle-based influenza vaccine using the PRINT technology. Nanomedicine. 2013; 9: 523-531.

46. Tan M, Jiang X. Norovirus P particle: a subviral nanoparticle for vaccine development against norovirus, rotavirus and influenza virus. Nanomedicine (Lond). 2012; 7: 889-897.

47. Babapoor S, Neef T, Mittelholzer C, Girshick T, Garmendia A, Shang H, et al. A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection. Influenza Res Treat. 2011; 2011: 126794.

48. Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013; 499: 102-106.

49. Yamashita I, Iwahori K, Kumagai S. Ferritin in the field of nanodevices. Biochim Biophys Acta. 2010; 1800: 846-857.

50. 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: 246-251.

51. 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: 265-273.

52. Girard MP, Cherian T, Pervikov Y, Kieny MP. A review of vaccine research and development: human acute respiratory infections. Vaccine. 2005; 23: 5708-5724.

53. Lamb RA, Choppin PW. Segment 8 of the influenza virus genome is unique in coding for two polypeptides. Proc Natl Acad Sci U S A. 1979; 76: 4908-4912.

54. Han T, Marasco WA. Structural basis of influenza virus neutralization. Ann N Y Acad Sci. 2011; 1217: 178-190 

55. Lamb RA, Zebedee SL, Richardson CD. Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface. Cell. 1985; 40: 627-633.

56. Zebedee SL, Richardson CD, Lamb RA. Characterization of the influenza virus M2 integral membrane protein and expression at the infected-cell surface from cloned cDNA. J Virol. 1985; 56: 502-511.

57. Holsinger LJ, Lamb RA. Influenza virus M2 integral membrane protein is a homotetramer stabilized by formation of disulfide bonds. Virology. 1991; 183: 32-43.

58. Holsinger LJ, Nichani D, Pinto LH, Lamb RA. Influenza A virus M2 ion channel protein: a structure-function analysis. J Virol. 1994; 68: 1551- 1563.

59. Takeuchi K, Lamb RA. Influenza virus M2 protein ion channel activity stabilizes the native form of fowl plague virus hemagglutinin during intracellular transport. J Virol. 1994; 68: 911-919.

60. Schotsaert M, De Filette M, Fiers W, Saelens X. Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines. 2009; 8: 499-508.

61. Ito T, Gorman OT, Kawaoka Y, Bean WJ, Webster RG. Evolutionary analysis of the influenza A virus M gene with comparison of the M1 and M2 proteins. J Virol. 1991; 65: 5491-5498.

62. Hughey PG, Roberts PC, Holsinger LJ, Zebedee SL, Lamb RA, Compans RW. Effects of antibody to the influenza A virus M2 protein on M2 surface expression and virus assembly. Virology. 1995; 212: 411-421.

63. Gabbard J, Velappan N, Di Niro R, Schmidt J, Jones CA, Tompkins SM, et al. A humanized anti-M2 scFv shows protective in vitro activity against influenza. Protein Eng Des Sel. 2009; 22: 189-198.

64. Treanor JJ, Tierney EL, Zebedee SL, Lamb RA, Murphy BR. Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. J Virol. 1990; 64: 1375-1377.

65. Zebedee SL, Lamb RA. Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions. J Virol. 1988; 62: 2762-2772.

66. Black RA, Rota PA, Gorodkova N, Klenk HD, Kendal AP. Antibody response to the M2 protein of influenza A virus expressed in insect cells. J Gen Virol. 1993; 74: 143-6.

67. Feng J, Zhang M, Mozdzanowska K, Zharikova D, Hoff H, Wunner W, et al. Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2. Virol J. 2006; 3: 102.

68. De Filette M, Ysenbaert T, Roose K, Schotsaert M, Roels S, Goossens E, et al. Antiserum against the conserved nine amino acid N-terminal peptide of influenza A virus matrix protein 2 is not immunoprotective. J Gen Virol. 2011; 92: 301-306.

69. De Filette M, Fiers W, Martens W, Birkett A, Ramne A, Löwenadler B, et al. Improved design and intranasal delivery of an M2e-based human influenza A vaccine. Vaccine. 2006; 24: 6597-6601.

70. Wolf AI, Mozdzanowska K, Williams KL, Singer D, Richter M, Hoffmann R, et al. Vaccination with M2e-based multiple antigenic peptides: characterization of the B cell response and protection efficacy in inbred and outbred mice. PLoS One. 2011; 6: e28445.

71. Mozdzanowska K, Feng J, Eid M, Kragol G, Cudic M, Otvos L Jr, et al. Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine. 2003; 21: 2616-2626.

72. Denis J, Acosta-Ramirez E, Zhao Y, Hamelin ME, Koukavica I, Baz M, et al. Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform. Vaccine. 2008; 26: 3395-3403.

73. Fiers W, De Filette M, El Bakkouri K, Schepens B, Roose K, Schotsaert M, et al. M2e-based universal influenza A vaccine. Vaccine. 2009; 27: 6280-6283.

74. Li R, Lim A, Ow ST, Phoon MC, Locht C, Chow VT, et al. Development of live attenuated Bordetella pertussis strains expressing the universal influenza vaccine candidate M2e. Vaccine. 2011; 29: 5502-5511.

75. De Filette M, Martens W, Roose K, Deroo T, Vervalle F, Bentahir M, et al. An influenza A vaccine based on tetrameric ectodomain of matrix protein 2. J Biol Chem. 2008; 283: 11382-11387.

76. Knossow M, Gaudier M, Douglas A, Barrère B, Bizebard T, Barbey C, et al. Mechanism of neutralization of influenza virus infectivity by antibodies. Virology. 2002; 302: 294-298.

77. Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem. 2000; 69: 531- 569.

78. Copeland CS, Doms RW, Bolzau EM, Webster RG, Helenius A. Assembly of influenza hemagglutinin trimers and its role in intracellular transport. J Cell Biol. 1986; 103: 1179-1191.

79. Laver WG. Separation of two polypeptide chains from the hemagglutinin subunit of influenza virus. Virology. 1971; 45: 275-288.

80. Taubenberger JK. Influenza virus hemagglutinin cleavage into HA1, HA2: no laughing matter. Proc Natl Acad Sci U S A. 1998; 95: 9713- 9715.

81. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science. 2004; 303: 1866-1870.

82. Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, Ha Y, et al. The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science. 2004; 303: 1838-1842.

83. Harrison SC. Viral membrane fusion. Nat Struct Mol Biol. 2008; 15: 690-698.

84. Bullough PA, Hughson FM, Skehel JJ, Wiley DC. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature. 1994; 371: 37- 43.

85. Pécheur EI, Sainte-Marie J, Bienven e A, Hoekstra D. Peptides and membrane fusion: towards an understanding of the molecular mechanism of protein-induced fusion. J Membr Biol. 1999; 167: 1-17.

86. Stegmann T. Membrane fusion mechanisms: the influenza hemagglutinin paradigm and its implications for intracellular fusion. Traffic. 2000; 1: 598-604.

87. Xu R, Krause JC, McBride R, Paulson JC, Crowe JE Jr, Wilson IA. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin. Nat Struct Mol Biol. 2013; 20: 363-370.

88. Fleury D, Barrère B, Bizebard T, Daniels RS, Skehel JJ, Knossow M. A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site. Nat Struct Biol. 1999; 6: 530-534.

89. Gerhard W, Mozdzanowska K, Zharikova D. Prospects for universal influenza virus vaccine. Emerg Infect Dis. 2006; 12: 569-574.

90. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011; 333: 850-856.

91. 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: 246-251.

92. Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, Yu W, et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011; 333: 843-850.

93. Chen J, Wharton SA, Weissenhorn W, Calder LJ, Hughson FM,Skehel JJ, et al. A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation. Proc Natl Acad Sci U S A. 1995; 92: 12205-12209.

94. Bommakanti G, Citron MP, Hepler RW, Callahan C, Heidecker GJ, Najar TA, et al. Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proc Natl Acad Sci U S A. 2010; 107: 13701-13706.

95. Wang TT, Tan GS, Hai R, Pica N, Ngai L, Ekiert DC, et al. Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proc Natl Acad Sci U S A. 2010; 107: 18979-18984.

96. Song L, Zhang Y, Yun NE, Poussard AL, Smith JN, Smith JK, et al. Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin. Vaccine. 2009; 27: 5875-5884.

97. Huleatt JW, Jacobs AR, Tang J, Desai P, Kopp EB, Huang Y, et al. Vaccination with recombinant fusion proteins incorporating Tolllike receptor ligands induces rapid cellular and humoral immunity. Vaccine. 2007; 25: 763-775.

98. Leng J, Stout-Delgado HW, Kavita U, Jacobs A, Tang J, Du W, et al. Efficacy of a vaccine that links viral epitopes to flagellin in protecting aged mice from influenza viral infection. Vaccine. 2011; 29: 8147- 8155.

99. McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983; 309: 13-17.

100. Brown LE, Kelso A. Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes. Immunol Cell Biol. 2009; 87: 300-308.

101. Staneková Z, VareÄ ková E. Conserved epitopes of influenza A virus inducing protective immunity and their prospects for universal vaccine development. Virol J. 2010; 7: 351.

102. Ben-Yedidia T, Arnon R. Design of peptide and polypeptide vaccines. Curr Opin Biotechnol. 1997; 8: 442-448.

103. Levi R, Arnon R. Synthetic recombinant influenza vaccine induces efficient long-term immunity and cross-strain protection. Vaccine. 1996; 14: 85-92.

104. Atsmon J, Kate-Ilovitz E, Shaikevich D, Singer Y, Volokhov I, Haim KY, et al. Safety and immunogenicity of multimeric-001--a novel universal influenza vaccine. J Clin Immunol. 2012; 32: 595-603.

Received : 02 Jul 2013
Accepted : 28 Jul 2013
Published : 14 Aug 2013
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X