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PubMed1996

Diversity among abortion strains of Chlamydia psittaci demonstrated by inclusion morphology, polypeptide profiles and monoclonal antibodies.

Twenty eight C. psittaci abortion strains had been previously classified in to 4 immunologically distinct groups on the basis of cross-protection experiments in a mouse model. To identify the molecular basis of their immunological divergence 4 representative strains were investigated by cellular, molecular and immunological techniques. An identical pattern was obtained by Alul digestion of the amplified major outer membrane protein gene (MOMP) by the polymerase chain reaction (PCR) of the 4 strains. However, inclusion morphology and polypeptide profiles clearly distinguished one strain, named LLG, and its homologous strain POS from the other prototypes by the presence of a unique protein at 26.5 kDa and the absence of a polypeptide at 23 kDa. Six out of 10 monoclonal antibodies (mAbs) raised against abortion strains failed to react with inclusions of the 2 strains. All 6 mAbs reacted with the chlamydial outer membrane complex (COMC). Two of these mAbs, one against the MOMP and one against an antigen at 90 kDa, did not react with immunoblots of LLG and POS. The data provide direct demonstration of the existence of strain variation in the field and classify strains LLG and POS as a distinct C. psittaci serotype 1-subtype. The antigenic diversity among abortion strains should be taken into consideration when designing a subunit vaccine.

Abortion, Veterinary↗

PubMed2004

Improving post-thaw survival of cryopreserved mouse blastocysts by hydrostatic pressure challenge.

The purpose of the experiments was to study the effect of high hydrostatic pressure treatment prior to vitrification to the survival of expanded mouse blastocysts. High hydrostatic pressure has been reported to induce the production of "shock proteins" in bacteria, which can provide a possibility of cross-protection to other environmental stresses. The possible beneficial effects of this alleged principle was examined on embryo vitrification. First, the behaviour of blastocysts was studied at altered pressure conditions. In the second part of the study, pressure treatment was combined with a cryopreservation protocol. Our results indicate that the survival of pressurized mouse embryos depends on the magnitude and the duration of pressure applied. We demonstrated that a preceding pressure treatment strikingly increases the survival of the frozen blastocysts as well as the speed of resumption of the development, and hatching rate.

Animals↗

PubMed2006

Update on viral accommodation, a model for host-viral interaction in shrimp and other arthropods.

Comparatively little published information is available on the mechanistic response of shrimp and other arthropods to viral pathogens. Much of the literature has been focused on the use of viruses for biological control of insect pests or disease vectors and on the use of baculoviruses as a means of heterologous protein expression in insect cell lines. The situation changed dramatically with the rapid global increase in cultivation of penaeid shrimp and the massive farm losses that have occurred due to viral pathogens. Urgency to solve these problems has led to a closer examination of the shrimp response to viral pathogens in the hope of finding new methods of disease control. Field observations and results of laboratory experiments in the past decade indicate that shrimp may be capable of a specific, adaptive response to viral pathogens that cannot be explained by current knowledge and understanding of their cellular and humoral defenses. Hallmarks of this response are specific tolerance to single and multiple viral infections without gross or histological signs of disease, a phenomenon common to crustaceans and insects. The concept of viral accommodation was introduced in 1998 as a simple testable hypothesis to explain these phenomena. Key elements of the hypothesis were an unknown mechanism for specific memory of pathogens and the role of this memory in dampening viral triggered apoptosis. Recent field and research results have supported predictions of the viral accommodation hypothesis and suggest that memory may be provided by the viral pathogens themselves in persistent infections that result in reduced severity of disease. The well-known phenomenon of defective interfering viral particles may play an important role in this process, but it cannot explain cross protection that has recently been described for heterologous viral infections. The major conclusion is that homologous and heterologous reduction in disease severity resulting from persistent viral infections (i.e., accommodated viral infections) may be a key process that has evolved from host viral interaction in the arthropod line.

Animals↗

PubMed2006

Changes in protein synthesis during thermal adaptation of Propionibacterium freudenreichii subsp. shermanii.

Dairy propionibacteria are present in Graviera Kritis, a traditional Gruyère-type cheese made without added propionic starter. Ten isolated strains were identified by a combination of SDS-PAGE, species-specific PCR and according to their ability to ferment lactose. They were all found to belong to the Propionibacterium freudenreichii subsp. shermanii species. Because of the stressing Gruyère technology, which includes cooking at 52 to 53 degrees C their thermotolerance was investigated at 55 degrees C. Thermotolerant and thermosensitive strains were clearly discriminated. Interestingly, the reference strain CIP 103027 belongs to the sensitive subset. One sensitive strain, ACA-DC 1305 and one tolerant, ACA-DC 1451, were selected for further study and compared to CIP 103027. For the sensitive strains ACA-DC 1305 and CIP 103027, heat pre-treatment at 42 degrees C conferred thermoprotection of cells at the lethal temperature of 55 degrees C, while there was less effect on the tolerant ACA-DC 1451. No cross-protection of salt-adapted cells against heat stress was observed for none of the strains. Differential proteomic analysis revealed distinct but overlapping cell responses to heat stress between sensitive and tolerant strains. Thermal adaptation upregulated typical HSPs involved in protein repair or turnover in the sensitive one. In the tolerant one, a distinct subset of proteins was overexpressed, whatever the temperature used, in addition to HSPs. This included enzymes involved in propionic fermentation, amino acid metabolism, oxidative stress remediation and nucleotide phosphorylation. These results bring new insights into thermoprotection in propionibacteria and the occurrence of divergent phenotypes within a same subspecies.

Adaptation, Physiological↗

PubMedDate not supplied

The development of the endoparasitoid Venturia canescens in Bt-tolerant, immune induced larvae of the flour moth Ephestia kuehniella.

We examined the survival and development of the endoparasitoid Venturia canescens in a Bt-tolerant laboratory strain of the flour moth Ephestia kuehniella, in which Bt-tolerance has been shown to be associated with an inducible elevation of the insect's immune response. The results indicate the elevated immune status associated with Bt-tolerance does not confer cross-protection against parasitism by V. canescens. No significant difference was observed in the rate of emergent wasps from parasitised Bt-tolerant and Bt-susceptible hosts. In addition, wasps from Bt-tolerant hosts had longer development times and were larger than wasps from Bt-susceptible hosts.

Animals↗

PubMed2025

Temporal and geographical lineage dynamics of invasive Streptococcus pyogenes in Australia from 2011 to 2023: a retrospective, multicentre, clinical and genomic epidemiology study.

BACKGROUND: Defining the temporal dynamics of invasive Streptococcus pyogenes (group A Streptococcus) and differences between hyperendemic and lower-incidence regions provides crucial insights into pathogen evolution and, in turn, informs preventive measures. We aimed to examine the clinical and temporal lineage dynamics of S pyogenes across different disease settings in Australia to improve understanding of drivers of pathogen diversity. METHODS: In this retrospective, multicentre, clinical and genomic epidemiology study, we identified cases of invasive S pyogenes infection from normally sterile sites between Jan 1, 2011, and Feb 28, 2023. Data were collected from five hospital networks across low-incidence regions in temperate southeast Australia and the hyperendemic, tropical, and largely remote Top End of the Northern Territory of Australia. The crude incidence rate ratio (IRR) of bloodstream S pyogenes infection comparing the Top End and southeast Australia and in First Nations people compared with non-First Nations people was estimated by quasi-Poisson regression. We estimated odds ratios (ORs) of intensive care unit (ICU) admission, in-hospital mortality, and 30-day mortality for the Top End versus southeast Australia using logistic regression. Retrieved and successfully sequenced isolates were assigned lineages at whole-genome resolution. Temporal trends in the composition of co-circulating lineages were compared between the two regions. We used an S pyogenes-specific multistrain simulated transmission model to examine the relationship between host population-specific parameters and observed pathogen lineage dynamics. The prevalence of accessory genes (those present in 5-95% of all genomes) was compared across geographies and temporal periods to investigate genomic drivers of diversity. FINDINGS: We identified 500 cases of invasive S pyogenes infection in patients in the Top End and 495 cases in patients in southeast Australia. The crude IRR of bloodstream infection for the Top End compared with southeast Australia was 5·97 (95% CI 4·61-7·73) across the entire study period; in the Top End, infection disproportionately affected First Nations people compared with non-First Nations people (5·41, 4·28-6·89). The odds of in-hospital mortality (OR 0·43, 95% CI 0·26-0·70), 30-day mortality (0·38, 0·23-0·63), and ICU admission (0·42, 0·30-0·59) were lower in the Top End than in southeast Australia. Longitudinal lineage analysis of 642 S pyogenes genomes identified waves of replacement with distinct lineages in the Top End, whereas southeast Australia had a small number of dominant lineages that persisted and cycled in frequency. The transmission model qualitatively reproduced a similar pattern of replacement with distinct lineages when using a high transmission rate, small population size, and high levels of human movement-characteristics similar to those of communities in the hyperendemic Top End. Using a lower transmission rate, larger population size, and lower levels of migration similar to those of communities in urbanised southeast Australia, the transmission model qualitatively reproduced a pattern of dominant lineages that cycled in frequency. Despite distinct circulating lineages, the prevalence of accessory genes in the bacterial population was maintained across geographies and temporal periods. INTERPRETATION: In a hyperendemic setting, the replacement of distinct S pyogenes lineages occurred in waves, which could be linked to the disproportionate burden of disease and sparse human population in this setting. The maintenance of bacterial gene frequency could be consistent with multilocus selection. These findings suggest that lineage-specific interventions-such as vaccines under development-should consider disease setting and, without broad cross-protection, might lead to lineage replacement. FUNDING: National Health and Medical Research Council, and Leducq Foundation.

Humans↗

PubMed2006

Infectious bronchitis virus serotypes in poultry flocks in Jordan.

Infectious bronchitis virus (IBV) causes respiratory disease in chickens all over the world. IBV has many serotypes that do not confer cross protection against each other. Hemagglutination inhibition (HI) test has been used to determine the serotypes of IBV as a substitute to the more laborious virus neutralization test and the more sophisticated restriction endonuclease digestion or sequencing of the S1 gene. In Jordan, no previous studies have been carried out to determine the involvement of IBV in respiratory disease in chickens, or the serotypes of IBV that possibly exist. In this study, serum from different chicken flocks (n=20) that suffered from respiratory disease were tested for IBV antibodies using commercial IBV antibody ELISA at time of the initial signs of the respiratory disease and repeated on serum samples from the same flocks 10-14 days later. ELISA titer for IBV increased in 14 out of 20 flocks (70%) after 10-14 days of the initial signs of the respiratory disease and this indicates a recent exposure to IBV. The second serum samples from these 14 flocks were further examined against a panel of five IBV antigens (Ark, Conn, DE-072, JMK, and Mass) by HI test to determine the serotype(s) of IBV they have been exposed to. The HI test results indicated that the exposure of some of these flocks were to Ark, DE-072, and Mass like serotypes. However, the HI titers against the antigens used in this study were relatively similar in 10 out of the 14 flocks (71%) and the serotype of IBV that these flocks were exposed to could not be determined and the possible causes of this are discussed.

Animals↗

PubMed2004

Differential antibody responses to a distinct region of human papillomavirus minor capsid proteins.

A peptide derived from the human papillomavirus type 16 (HPV-16) minor capsid protein, L2, has previously been reported to induce cross-neutralizing antibodies in mice. In this report, four HPV L2 peptides, including the HPV-16 peptide and its HPV type 6 and 11 homologues, along with extended peptides containing a conserved set of amino acids, were used to immunize rabbits and mice. Antibody responses were evaluated for specificity and ability to neutralize viral infection in vitro with a quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) assay. All peptide immunizations resulted in cognate and cross-peptide reactivity, but this did not translate equally into recognition of full-length protein, VLP, or neutralization of virus in vitro. This report provides the first evidence of cross-neutralization of authentic HPV by antiserum to L2 peptides. Comparison of the anti-peptide serum reactivity, especially with regard to neutralization of virus, indicates that the extended peptides may offer more potential to induce adequate responses for cross-protective immunity.

Animals↗

PubMed2004

Immunogenicity of polyepitope libraries assembled by epitope shuffling: an approach to the development of chimeric gene vaccination against malaria.

Developing a polyepitope vaccine which contains diverse antigenic types is a promising strategy to cope with the problem of malaria variation and diversity. However, arranging the peptides to produce the most effective immunogenicity remains a hurdle. In an attempt to develop an effective complex antigenic gene vaccine, we constructed a polyepitope library by randomly assembling epitopes using the epitope shuffling technique. The polyepitope library, which contains epitopes from different antigens of Plasmodium falciparum, was divided into five sub-libraries based on the size of chimeric genes. Here we report that higher antibody titers were observed in mice with immunized with sub-libraries containing genes >1200 bp, using enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IFAT) assay to determine both individual epitope peptides and the natural parasites at the erythrocyte stage. Different levels of IgG subtypes and cytokines were elicited by different sub-library and administration times. In a rodent malaria model, some groups of immunized mice were partially cross-protected against a lethal challenge from Plasmodium yoelii. These results suggest that the immunogenicity of a polyepitope chimeric antigen is essentially conformation- and length-dependent, and demonstrates that the promising advantage of epitope shuffling technology is that it allows us to randomly assemble many polyepitope molecules in tandem format. This finding also indicates that polyepitope library vaccination is a suitable approach for screening optimized chimeric gene vaccines against malaria and other diseases.

Animals↗

PubMed2005

Anticipating crisis: towards a pandemic flu vaccination strategy through alignment of public health and industrial policy.

Flu pandemics (worldwide epidemics) have occurred at irregular and unpredictable intervals, and have been associated with substantial morbidity, mortality and economic cost. In response to the emerging potential for a new pandemic to occur, national and international preparedness plans are being drawn up specifying the use of antivirals and vaccines. A number of challenges to pandemic vaccine development, large-scale production and the timing of distribution have also been highlighted. This article reviews the rationale and consequential policy for aligned public- and private sector planning in the present inter-pandemic period despite the prevalent risks and uncertainties. We propose a model for product development of pandemic flu vaccine based on public-private partnership, including push and pull incentive mechanisms for stimulating work in this therapeutic area. In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection.

Disease Outbreaks↗

PubMed2006

Estimating vaccine effectiveness against laboratory-confirmed influenza using a sentinel physician network: results from the 2005-2006 season of dual A and B vaccine mismatch in Canada.

INTRODUCTION: We report a case-control design using a sentinel physician network to estimate vaccine effectiveness (VE) against laboratory-confirmed, medically attended influenza (LC-MAI) and provide results for the 2005-2006 season of dual A and B vaccine mismatch in Canada. METHODS: Participants were patients >or=5 years of age presenting with influenza-like illness (ILI) to a sentinel physician in British Columbia, Canada between November 1, 2005 and April 30, 2006. Cases were participants in whom influenza was identified; controls tested negative for influenza A and B by PCR, R-mix and culture. Isolates were characterized by gene-sequencing and hemagglutination-inhibition (HI) assays. Odds ratios (OR) for LC-MAI in vaccinated versus non-vaccinated persons were derived with adjustment for age and chronic conditions. VE was estimated as [1-OR (vaccinated/unvaccinated)]. RESULTS: The sample included 442 patient visits: median age was 26 years, 10% were >or=65 years, 15% had a chronic condition and 22% received the 2005-2006 trivalent inactivated influenza vaccine >or=2 weeks before ILI onset. Two hundred and six participants were positive for influenza; 107 (52%) had influenza A/H3N2 and 99 (48%) had influenza B/Victoria lineage. Gene sequencing identified mutations away from the vaccine strain at key antigenic binding sites of the hemagglutinin (HA) protein of H3N2 isolates; the neuraminidase (NA) protein was conserved. Based on HI assays, three-quarters of influenza A and all B isolates were mismatched to the 2005-2006 vaccine. Point estimates for VE against LC-MAI were in the range of 50 to 70% for both types of influenza. CONCLUSION: 2005-2006 was the third consecutive season of vaccine mismatch based on varying HA for the A/H3N2 component and the third also for the B component since 2001. Vaccine mismatch resulted in diminished VE but substantial cross-protection. More timely detection of drift variants through gene sequencing of isolates facilitates interpretation of VE results. Since it may be more antigenically conserved, the vaccine content and contribution of NA to overall VE should be further evaluated for both A and B components. Infrastructure for real-time epidemiologic assessment of vaccine performance is important annually and in preparation for a pandemic.

Adolescent↗

PubMed2006

Vaccination of chickens against Campylobacter.

The gram-negative bacterium Campylobacter is the leading cause of bacterial entero-colitis in humans and is associated with the occurrence of life-threatening auto-immune based neurological disorders. Chickens, which are often heavily colonized with Campylobacter without signs of pathology, are considered the most important source for human infection. Although vaccination is a well established and effective method to combat various microbes in poultry, a commercial vaccine against Campylobacter has not yet been developed. For the development of such a vaccine, three main challenges can be identified: (1) the identification of novel cross-protection-inducing antigens, (2) the induction of a rapid, potent immune response, and (3) the development of novel adjuvants to further stimulate immunity against Campylobacter. The rapidly emerging knowledge of the biology of Campylobacter in combination with the recent advances in the fields of molecular vaccinology and immunology provide the required setting for the development of an effective vaccine against Campylobacter in poultry.

Animals↗

PubMed2004

Molecular conservation of MSP4 and MSP5 in Anaplasma marginale and A. centrale vaccine strain.

Anaplasma centrale msp4 and msp5 genes were cloned and sequenced, and the recombinant proteins were expressed. The identity between Anaplasma marginale and A. centrale MSP4 was 83% in the nucleotide sequences and 91.7% in the encoded protein sequences. A. centrale msp5 nucleotide sequences shared 86.8% identity with A. marginale msp5, and there was 92.9% homology between A. centrale and A. marginale encoded amino acids of the MSP5 protein. Southern blots hybridized with probes derived from the msp4 and msp5 central regions indicate that msp4 and msp5 of A. centrale are encoded by single copy genes. Recombinant MSP4 and MSP5 fusion proteins reacted with anti-A. marginale monoclonal antibodies ANAR76A1 and ANAF16C, respectively, demonstrating the conservation of conformation-sensitive B-cell epitopes between A. centrale and A. marginale. These data demonstrate the structural and antigenic conservation of MSP4 and MSP5 in A. centrale and A. marginale. This conservation is consistent with the cross-protective immunity between A. marginale and A. centrale and supports the development of improved vaccines based upon common outer membrane proteins.

Amino Acid Sequence↗

PubMed2004

DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1.

DNA vaccines expressing the envelope (Env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, DNA vaccines were constructed to express a fusion protein of the soluble human CD4 (sCD4) and the gp120 subunit of the HIV-1 envelope. To enhance the immunogenicity of the expressed fusion protein, three copies of the murine C3d (mC3d3) were added to the carboxyl terminus of the complex. Monoclonal antibodies that recognize CD4-induced epitopes on gp120 efficiently bound to sCD4-gp120 or sCD4-gp120-mC3d3. In addition, both sCD4-gp120 and sCD4-gp120-mC3d3 bound to cells expressing appropriate coreceptors in the absence of cell surface hCD4. Mice (BALB/c) vaccinated with DNA vaccines expressing either gp120-mC3d3 or sCD4-gp120-mC3d3 elicited antibodies that neutralized homologous virus infection. However, the use of sCD4-gp120-mC3d3-DNA elicited the highest titers of neutralizing antibodies that persisted after depletion of anti-hCD4 antibodies. Interestingly, only mice vaccinated with DNA expressing sCD4-gp120-mC3d3 had antibodies that elicited cross-protective neutralizing antibodies. The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d.

AIDS Vaccines↗

PubMed2004

Markedly reduced severity of Dengue virus infection in mosquito cell cultures persistently infected with Aedes albopictus densovirus (AalDNV).

AalDNV-infected C6/36 cells serially passaged for over 10 weeks showed a decline in percentage of anti-AalDNV-positive cells (APC) from an initial 92% to approximately 20%. Cultures of persistent APC were indistinguishable from uninfected cultures by direct microscopy but most stained cells from early APC passages had enlarged nuclei with eosinophilic inclusions, while late APC passages had few and naive cells none. Super challenge of persistent APC cultures did not increase percentage APC and supernatants from persistent APC cultures gave low APC (40%) in naive C6/36 cell cultures. When challenged with dengue virus serotype 2 (DEN-2), naive C6/36 cells showed severe cytopathic effects (CPE) and high mortality within 4 days, as did early passage APC cultures. Remarkably, DEN-2 infections in persistent APC cultures were much less severe, being characterized by reduced DEN-2 infection percentage, retarded DEN-2 virion production, no CPE and no significant mortality. Reasons for rapid reduction in APC and resistance to superinfection upon serial passage remain unproven but may relate to production of AalDNV-defective interfering particles (DIP) by molecular mechanisms still open to speculation. More difficult to explain is cross-protection against DEN-2-induced mortality seen in persistent APC cultures. However, by comparison to work on shrimp viruses, we speculate that this may involve blockage of viral-triggered apoptosis. The phenomena described raise questions regarding the potential for persistent infections by unknown viruses to confound experimental results with insect cell lines.

Aedes↗

PubMed2006

Cross-reactive CTL recognizing two HLA-A*02-restricted epitopes within the BK virus and JC virus VP1 polypeptides are frequent in immunocompetent individuals.

Two HLA-A*02-restricted epitopes have been identified within the VP1 polypeptide of a human polyomavirus, BK virus, which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Immunization of transgenic mice with recombinant modified vaccinia Ankara expressing BKV VP1 (rMVA-BKV VP1) elicited functional CTL populations recognizing the sequences LLMWEAVTV (amino acids residues 108-116, BKV VP1p108) and AITEVECFL (residues 44-52, BKV VP1p44) and cross-reactive to the previously described JC virus VP1 homologs. Flow-based analyses of PBMC from a panel of thirty healthy HLA-A*02 human volunteers indicated that the majority of these subjects harbored functional CTL populations recognizing the BKV epitopes and cross-reactive with the JCV homologs. CTL recognizing the JCV VP1p100 and JCV VP1p36 epitopes have previously been associated with prolonged survival in progressive multifocal leukoencephalopathy patients. These findings suggest that infection with BKV or JCV could potentially induce cross-protective T-cell immunity against diseases associated with these viruses.

Animals↗

PubMed2006

Identification of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry.

Using site-directed mutagenesis and retroviral vector pseudotyping of the wild type or mutated glycoprotein of Zaire ebolavirus (ZEBOV), we analyzed 15 conserved residues in the N-terminus of the filovirus glycoprotein 1 (GP1) in order to identify residues critical for cell entry. Results from infectivity assays and Western blot analyses identified two phenylalanine residues at positions 88 and 159 that appear to be critical for ZEBOV entry in vitro. We extended this observation by introduction of alanines at either position 88 or 159 of Ivory Coast Ebolavirus (CIEBOV) and observed the same phenotype. Further, we showed that introduction of each of the two mutations in a recombinant full-length clone of ZEBOV (Mayinga strain) that also carried the coding sequence for GFP could not be rescued, suggesting the mutants rendered the virus non-infectious. The two phenylalanines that are critical for both ZEBOV and CIEBOV entry are found in two linear domains of GP1 that are highly conserved among filoviruses, and thus could provide a target for rational development of broadly cross-protective vaccines or antiviral therapies.

Amino Acid Sequence↗

PubMedDate not supplied

Entamoeba histolytica: sequence conservation of the Gal/GalNAc lectin from clinical isolates.

The Gal/GalNAc lectin gene of Entamoeba histolytica is a major amebic virulence protein responsible for interaction with host tissues. We investigated sequence differences in the Gal/GalNAc lectin heavy subunit in three isolates from Bangladesh and one isolate from Georgia, each of which was determined to be genetically distinct by SREHP AluI digestion. Interestingly, we observed only slight genetic diversity in the lectin gene as compared with the HM1:IMSS laboratory strain, originally a clinical isolate from Mexico. Genetic conservation of the Gal/GalNAc lectin between isolates may reflect that the lectin is under strong functional selection or possibly, that E. histolytica is a clonal population. Sequence conservation of the lectin indicates that immune responses against it should be cross-protective.

Amino Acid Sequence↗