Since the down of human civilization that might begin with Chinese and Indian tradition in curing human as well as animal diseases
they had had been using variety of remedies (Therapeutics) originated from both animal and plant resources. The human need for therapeutics
led him almost always searching for new preparations . Now it is being an opportunity to gather hetero-genus preparations
in a group-wise fashion as that of vaccine like, standard or standardized immune-biologics which have some features of vaccines in
one proposed group designated as therapeutic vaccine allied biologics(TVAB) .To date it is being evident the proposal holding that at
least there are five classes of(TVAB) available both at experimental level and to a lesser extent to the level of clinical use .The classes
are as; cellular secretions(cytokines ,antibodies) ,receptor-anti-receptor(immune check point inhibitors) , subunit macromolecules (Beta
Glucan) and commensal microbiome( probiotics) and Bacterio-therapeutics( cancer killing bacteria) . These proposed classes were
evaluated by vaccine criteria as well as by a group specific special evaluation criteria ,collectively ,it is being a state of developing a
novel evaluation system. They are helpful as therapeutics for ;microbial ,envenomation ,immune mediated and neoplastic diseases
with variable degrees of success .
Antibody, Bacterio-therpeutics, Biologics, Cellular, Cytokine, Experimental Vaccine
There are hetero-genus standard and standardized immunebiologics
that are similar to vaccine in few or more of their
features and /or their evaluation criteria exhibiting therapeutic
potentials both at the levels of experimental animal models and
human beings .In a previous communication it was designated
as vaccine allied biologics.When we combine their therapeutic
potentials, the designation will be” Therapeutic Vaccine Allied
Biologics”[TVAB].In the present opinion attempts were made
to :i- Review their features, ii- build up an evaluation criteria
for their safety and efficacy and iii-Propose a classification that
Class I : Cellular Secretions:
Cytokines are secretory hormone-like peptides or low molecular
weight secretory proteins synthesized and produced by vertebrate
nucleated cells like lymphocytes, macrophage ,adipocyte and
epithelial cells. They are classified[2,3]
into innate ,adaptive immune
cytokines ,primary inflammatory, secondary inflammatory
,inflammatory and anti- inflammatory cytokines .They forms a
chemical language in networking fashion for signal transduction
among immune and nonimmune cells and own divers roles
in immune homeostasis ,heamopoiesis ,regulation of immune
and inflammatory responses Cytokines are essential biologics
for medical oncology. Colony stimulating factors are of use to
protect the bone marrow precursor expansion. Cytokine like
type I interferon and IL2 are in common use as antitumor agents
such as ;lymphomas ,multiple myeloma, renal cell carcinoma and
melanoma .Unwanted co-effects are evident in case of use of IL12
as anti-tumor drug has been shown toxicity to the patients
Antibodies are either of polyclonal or monoclonal nature.They
are globular glycoprotein that found in gamma globulin area of
serum electro-phoro-gram of human beings. The immunoglobulins
gain their specificities to certain infectious agents ,synthesized
and produced from B lymphocyte within the lymphoid organs on
instu antigen stimulations. They are specific polyclonal ,since are being as net result of multiple epitope stimulations of B
An antigen was tempted to specific immune priming of mice using
multiple dosage program in a week a part for three weeks .One
week leave then the primed mice were eviscerated ,spleen saved
,macerated, and splenocyte separated .Now these splenocytes are
antigen primed. myeloma lymphocyte cell line was screened for
vitalty and co-cultured with these antigen primed splenocytes in
cell culture with HRPTG to grow up the hybridoma cell which
produce daughter cell that grown in separate cultures in which they
form clones that are able to produce specific antibody homogenous
physico-chemically ,genetically and immunologically such
antibody is known as monoclonal antibody .Monoclonal antibody
has diagnostic ,therapeutic ,immunologic and genetic uses
Antibody in Practice:
Serum technology means the techniques and assays available
for making ,standarizing ,dispensing, releasing and marketing of
immune sera. These sera are of main three classes ;immune animal
sera ,immune human sera and hyper-immune globulins .Disease
states that needs the use of therapeutic sera are depicted in Table
1,tests for biological standardization of therapeutic sera are being
detailed in Table 2.While the licensed therapeutic immune sera
are tabulated in Table 3.[4,5 ]
Host- Immune Sera interactions:
In the immunologic sense the host-immune sera interactions
means that there are epitopes within the immune sera can be as
neutralization of virus ,toxin or venom as the possible immune
reactions such as the allergenic responses due to the animal
derived epitopes within the immune sera which appeared as
atopic or serum sickness reactions.
Anti-cytokines are rather in common use for some disease
conditions .Studies have shown that the anti-TNF ,anti-IL6 and
anti-IL5 are evident in antibodies have clinical practice. However
,Anti-TNF alpha have been excessively investigated both in
laboratory animals and in man for bacterial ,parasitic and autoimmune
diseases and found to be protective Table 4.The unwanted
co-effect seen is vulnerability to infection and autoimmune
Table 2: The tests usable in biological standardization of therapeutic sera.
Class II : receptor-anti-receptor: Immune Check Point Inhibitor:
It is a check point protein ,program death 1 PD1 recognize
two legends PDL-1,and PDL-2.PDL-1 expressed on antigen
presenting cells APC and many other tissues.PDL-2, expressed
mainly onto APC. Engagement of PDl-1 by either legend
leads to inactivation of T cells .Specific antibody to PDL-1 or
its legend is effective in enhancing cancer killing T cells in mice
.Several human trails have shown that PD-1 or PDL-1 blockade
can limit tumor progression and reduces tumor burden in patients
with advanced cancer .Such blocked can be established through
the use of monoclonal antibody specific to PD-I or PDL-1or
PDL-2..Check point inhibitors seek to overcome one of cancer
cell main defense against the host immune system and help to
keep the immune response under check. Unwanted co-effects are
autoimmune disease and inflammatory reactions.
Class III : Subunit macro-molecules:
Beta glucans are glucose polymers forming parts of cell wall of
certain pathogenic bacteria and fungi .They are naturally occurring
poly-saacharides. Beta glucans derived from different sources
have shown some differences in their structures .Glucans are
heterogenous group of glucose polymers consisting a back bone of
B(1,6)-linked B-D-B(1,6)- with variable length and distributions.
Beta glucans exhibit an anti-infective protective influences against
;Staphylococcus aureus ,Escherichia coli ,Listeria monocytogenes
,Pneumocystis carini ,Candida albicans and Influenza virus .It is an
anthrax protective in mice model .It has been tested for safety and
efficacy in surgical patients at high risk for postoperative infections
.Dose response relations for different grades of concentrations
have been tested.
Beta glucan as a hapten has shown to be of poor immunogenicity
.Conjugation with carrier protein made it immunogen and found
protective against filamentous fungal pathogen in laboratory
animal model. Protection seems to due to anti-glucan antibodies
and never be used as a vaccine[10,11].
The features of glucan immune functions are being as ;i-activating
complement system ,enhance macrophage function ,ii- augment
natural killer cell functions and iii- the induction of cellular
immune responses as well as iv-powerful antitumor agent.
Class IV : Commensal microbiome:
Probiotics are commensal bacteria and commensal yeasts ,that are of
diverse biologic potentials .Probiotic technology covers the theme
of selection of strains ,preparation of starters ,studying the strain
physiology and strain immune potentials as well as cell techniques
.Probiotics displayed their preventive and /or therapeutic effects
through their immunogenicity, immune-adjuvant, and tumor
reducing activities.The immune features can be through;Antiinflammatory,antiautoimmune,anti-cancer,immunoadjuvant and vaccine delivery system.Upon trying to apply vaccine
evaluation criteria on probiotics it showed rather similar criteria
but less stringent in preparation schemaz.No reported unwanted
co-effects on using probiotics.
Class V : Bacterio-therapeutics( Cancer Killing Bacteria):
Some bacterial pathogens like Streptococcus pyogenes has the
anti-cancerous potentials in their natural state. Others ,however
,own such potentials after getting modification in their genetic
constitutions. Two examples of genetically modified bacteria to
be active as cancer killer bacteria and are being briefed[15,16] in the
1-Synchronizing bacterial lysing strains that have the ability of an
in-vivo delivery system that grow and release cytotoxic agents insitue
which acts as circuit engineered bacteria.
2-Salmonella typhimurium auxotroph AI-R that were genetically
engineered to grow in viable, and necrotic tumor tissue as well as
kill tumor cells in laboratory animal models .Human trails are
The licensed vaccine affairs for human and animals upon used
as immune-prophylactants for mass vaccination programs
were briefed in[17,18].Likewise, Experimental developed vaccine
for human welfare were presented in.What concerned with
probiotics were reviewed by Shnawa.Cell based vaccines was
reviewed in.Vaccine allied biologics typified by probiotics was
characterized in brief through the editorial Shnawa.In the present
opinion tempts were made to review in brief the therapeutic vaccine
allied biologics focusing onto; i-Brief feature ,ii-build up oriented
evaluation criteria,Table 5,6., as well as iii- propose a classification
system to them ,Table 7.
Therapeutic Vaccine Allied Biologics In Brief:
It is hetero-genus group of biologics that interplayed vaccine
like potentials in both laboratory animals and man .It covers
cellular secretions, subcellular, subunit macromolecules and whole cells. They , ensemble in five major classes as; Cellular secretions [cytokine ,antibodies, receptor-anti-receptor [immune check point inhibitors], subunit macromolecules [beta glucan], commensal microbiome [probiotics] and bacterio-therapeutics [cancer killing bacteria]. They are helpful as therapeutic agents for;Infections, autoimmune and neoplastic diseases .The evaluation criteria for such products subjected to that of preventive ,in
addition to those that are specific to the disease.
- Shnawa IMS,2016,Vaccine allied biologics, IJVV ,2(2):00024.
- Shnawa IMS,2016, Oral Epithelial cytokines,IJVV,2(2):00026.
- Mantovani A, Dinarello CA , Ghezzi P,2000,Pharmacology of
Cytokines,Oxford university Press,Oxford,233-237.
- Roitt I,Brostoff J,Male D,2001,Immunology 6th
- Banker DD,1982,Modern Practice In Immunization ,Popula
- Abraham E, Wudrink R , Silverman H et al., 1995, Efficacy and safety of monoclonal antibodies to TNF alpha with systemic syndrome.A randomized double blind ,multicenter clinical trials, JAAMA,273;934-941.
- Abbas AK ,Lichtman NH ,Pillai ,2013,Cellular And Molecular
Immunology ,Elseveirs Saunders,Philadelphia,321,391.
- Bromuro ,Torosantucci P ,Chainict P,Conti S,Polonelli L Casson
A ,2002, Interplay between protective and inhibitory antibody dictates the outcomes of experimentally disseminated candidiasis in relation to Candida albicans vaccine,Inf.Immun.,70:5462-5470.
- Torosatucci A ,Bornuro C, Chiani P ,De F,Berti F,Galli C
,Norelli F,Bellucci C,2005, A Novel glycol-conjugate vaccine
against fungal pathogens,J.Exp.Med.,202:597-606.
- Babineau TJ,Marceas P,Swails W,Kenler A,Bistian B, frose RF,1994,randomized PhaseI/II trials of macrophage PGG glucan in high risk surgical patients.,Arch.Surg.,230:601-609.
- Babinaeu TJ,hackfor A ,kenler A,Bristian B, Frose RA faircheld
PG et al.1994,A phase I multicenter randomized plcebo controlled study of three dosage of PGGglucan in high risk surgical patients,Arch.Surg.,129:1204-1210.
- Akramanone D,Kondrotas A,Didziapetriene J,Kerelaitis
E,2007, Effect of Beta glucan on the immune system,Medicinia (Kaunas),43(8):597-606.
- Reid G,1999, Scientific bases for probiotic strains of lactobacilli. ,Appl.Env .Microbiol .65(9):3763-3766.
- Shnawa IMS,2016,The Immune Potentials of
- Omar Din M ,Danino,T,,Prindle A ,Skalak M ,Selimkhanov
J,Allen E,Atolia E,Bhatia SN,Hasty J,2016, Synchronized cycles
of bacterial lysis in-vivo delivery,Nature 636:81-85.
- Uchuonova A , Zhao M , zhang Y,Weinigel M,Kong K ,Hoffman
RM ,2012, Cancer killing Salmonella imaged by multiphoton Tomography in live mice,Anticancer. Res.32:4331-4338.
- NIH,1998, Understanding Vaccines,NIH,Publication No.98-4219,23.
- Shnawa IMS,2016,Vaccinology At A Glance,Lap lambert
- Shnawa IMS 2016,Vaccinology Letters :A Treatise Concerning
The Experimental Vaccine ,IITE,USA.
- Shnawa IMS,2017,Dendritic Cell based Vaccine for human
- Lorenzo-Gomez MF ,Padilla-fernandez B,Garcia-Cardin
FJ,Miron-Canella JA,Gii-Viceenle A ,Nito-Huerotes A ,SilvaAbuin
JM,2013. Evaluation of therapeutic vaccines for prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics,Int..Urogynecol.J.,24:127-134.
- Spaans JN,Routy J-P,Trembaly C, et al.,2012,Optimizing the
efficiency of therapeutic for HIV vaccine trial :A case for CTN
123,Trials In Vaccinology,1:21-26.
- riva A,Hohl TM,2015, Calnexin Bridges the gap toward a panfungal vaccine,Cell-Host and Microbes,17:421-423.
- Nanjappa SG,Kelin BS,23014, Vaccine –immunity against fungal infection, Curr.Opin.Immunol.,28:27-33.
- Wolchok JD,Hoos A,ODay S, et al.,2009, Guidelines for the
evaluation of immunotherapy activity in solid tumors,Immune