




































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: drasv@ymail.com; 
 
 
 

Asian Journal of Immunology 
 
3(1): 61-70, 2020; Article no.AJI.55881 
 

 
 

 

 

Local Immunity Concept in the Context of the  
Novel Corona Viral Infection: A Consideration 

 
A. S. V. Prasad1* 

 
1
Department of Internal Medicine, Gandhi Institute of Technology and Management, Rishikonda, 

Visakhapatnam, India. 
 

Author’s contribution 
 

The sole author designed, analysed, interpreted and prepared the manuscript. 
 

Article Information 
 

Editor(s): 
(1) Darko Nozic, University of Belgrade, Serbia. 

Reviewers: 
(1) Wuyi Liu, Fuyang Normal University, China. 

 (2) Vijaya Krishnan, MGM College of Physiotherapy, India. 
 (3) M. Zamri Saad, Universiti Putra Malaysia, Malaysia. 

Complete Peer review History: http://www.sdiarticle4.com/review-history/55881 

 
 
 
 

Received 20 March 2020  
Accepted 30 March 2020 
Published 01 April 2020 

 
 

ABSTRACT 
 

The pandemic of novel corona virus disease (covid 19), is presently sweeping the world over. The 
causative virus is named, SARS-CoV-2. The rapidity with which the pandemic is advancing is 
catastrophic. That there is no known treatment for this killer disease is throwing public at large into 
a state of fear psychosis. The urgent need for preventive vaccine is felt now, more than ever before 
Though promising research is going on, the goal to achieve a breakthrough vaccine is still a long 
way to go. Since SARS-CoV-2 is an infection restricted to respiratory system of the affected, 
vaccines aimed at inducing local (mucosal) immunity may offer better chance of preventing the 
acquisition and spread of the disease to others, than induction of systemic immunity. With this 
background theme, this article briefly reviewed the epidemiology, the vaccine trials of the Covid 19 
as well as the immune responses to viral infection in general and with a special focus on the 
concept of Local immunity advanced by Prof Besredka (1924). The historical perspective of the 
local immunity concept is recapitulated and the diseases, both viral and bacterial, to which vaccines 
are developed in the past basing on this concept are reviewed. A case is made out for applying this 
concept for the prevention of covid 19. It is suggested that an approach to boost local immunity, 
than systemic immunity, might be a better strategy of prevention of covid 19. 

 

 

Opinion Article 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
62 

 

Keywords:  Covid 19; local immunity; viral immunity; sars-cov-2(severe acute respiratory syndrome- 
corona virus 2); mers-cov(middle east respiratory syndrome coronavirus). 

 

1. INTRODUCTION  
 
1.1 Epidemiological Considerations of 

Covid 19 
 

 The massive awareness programme 
against the Covid 19 world over,                   
made any introduction to this disease 
superfluous. Similarly the rapid changes 
from day to day of statistical data made 
any cited data meaningless, in no time. 
Nevertheless, convention demands brief 
introduction to the disease. A pneumonia 
of unknown cause detected in Wuhan, 
China was first reported to the WHO 
Country Office in China on 31 December 
2019.The outbreak was declared                        
a Public Health Emergency of   
International concern on 30 January 2020. 
On 11 February 2020, WHO                 
announced a name for the new 
coronavirus disease. The strain involved is 
considered novel as it is different from 
corona virus strains that are known before 
and hence. 

 The name covid 19. SARS-CoV-2 belongs 
to the Beta coronavirus Genus, which also 
includes SARS CoV (2003) and MERS 
CoV (2012). SARS-CoV first emerged in 
2002-2003 in Guangdong, China as an 
unusual pneumonia, that caused life-
threatening respiratory failure in certain 
cases. It quickly became pandemic. 
MERS-CoV epidemic appeared in Saudi 
Arabia in 2012, with people experiencing 
similar symptoms to SARS-CoV but dying 
at a much higher rate of 34 per cent. 
Unlike SARS-CoV, which spread quickly 
and widely, MERS-CoV has been mainly 
limited to the Middle East. On 11 February, 
the novel coronavirus that had 
provisionally been known as 2019-nCoV, 
was given a new name, SARS-CoV-2. The 
acronym SARS stands for severe acute 
respiratory syndrome. Cov2 stands for 
corona virus 2. The name denotes its close 
relationship to the SARS virus. According 
to WHO report as on 18

th
 march 2020, the 

total globally confirmed cases are 1,90,415 
and total confirmed deaths are 7, 800. As 
on March 23,2020 the total number of 
cases and total deaths globally are 
respectively, 292142 and 12784  WHO, 

data as on 24 march 2020 is total number 
of cases-372757, deaths 16,231 and 
countries infected are 195. As on 30 March 
2020, 715 660 cases have been          
reported. 

 Including 33 579 deaths. The speed with 
which the disease is spreading can be 
inferred from the above figures. The 
mortality rate is between, 1 t0 3% The 
economic loss due to covid 19 as 
estimated in the beginning of march 2020 
is about 1 to 3 trillion dollar. Trade and 
tourism, world over are worst effected. It is 
considered as a zoonotic infection, 
reservoirs being the wild bats and certain 
snakes. The infection starts like flu with 
cold and dry cough and fever. Soon 
shortness of breath occurs with developing 
pneumonia and the patient may require 
ventilator support. While cold and flu 
viruses take 2-3 days to develop once you 
contract the virus, coronavirus symptoms 
take anywhere from 2-14 days after being 
exposed to the virus, as per the Centres of 
Disease Control and Prevention (CDC). 
According to a study (March 10, 2020). 
The transmission from man to man is 
through direct spread by droplet infection 
and indirectly by coming into contact with 
objects on which the virus containing 
infective material is deposited. The survival 
of the virus outside the human host is 
variable, depending on the material 
concerned ranges from 1 to 5 days. The 
estimated median of IP is 5.1 days. 
Comorbid conditions in general and 
respiratory diseases like Asthma/ COPD 
as well as old age appear to be the risk 
factors at the individual level. Women and 
children are mostly spared, but not 
completely. Presently thereisno specific 
drug against the virus is available, so, the 
present emphasis is on prevention of the 
spread of the infection. Home isolation of 
the suspected cases, qwarentaining the 
positive cases, social isolation and self 
imposed curfew are some of the strategies 
adopted, which are showing promising 
results. Some retrovial drugs and Hydroxy 
chloroquin T-Azithromycine combination 
are used emparically. There is intense 
research going on to find a vaccine against 
the disease.  

 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
63 

 

1.2 Can Covid 19 be Transmitted by 
Asymptomatic Carriers? 

 

Zhang et al. [1] have reported a familial cluster of 
COVID-19 indicating virus can be transmitted by 
asymptomatic carriers. AnBai’s study presumed 
that asymptomatic 2019 nCoV carrier could be a 
transmitter. [2] A couple with COVID-19 were 
transmitted infection by their asymptomatic 
daughter who had travelled from the epidemic 
center of Wuhan. The sequence suggests that 
the coronavirus can be transmitted by 
asymptomatic carriers in their early and middle 
latent period. Asymptomatic virus carriers should 
be monitored and isolated as early as possible to 
facilitate the control of the epidemic. A paper 
published on NEJM about the first four people in 
Germany infected with 2019 nCoV found 
asymptomatic persons can still transmit the virus 
to others [3] but soon the German government’s 
public health agency announced that the 
information was wrong. The “asymptomatic” 
patient actually had some symptoms, it was 
found later [4]. 
 

1.3 Are There Two Strains of the Novel 
Corona Virus? 

 

At the outset it is made clear that the WHO has 
not at accepted the 2 strains concept as on now. 
Since some investigators found two types of 
mutations in the genome of the Covid                               
virus (see below) and few investigators tried to 
see difference in virulence patterns of the               
same virus at different geographical places, (for 
instance the infection is catastrophic in                     
Italy, but so far appears to be comparatively, mild 
in India) hazard a guess about the existence of 
more virulent and less virulent strains of the 
covid 19 virus. It is probable that the                  
deficiency of timely interventional measures 
might be the cause, as felt in case of Italy.  
Xiaolu Tang et al, at Peking University in                
Beijing and his colleagues studied the viral 
genome taken from 103 cases. They found 
common mutations at two locations on the 
genome. The team identified two types                         
of the virus based on differences in the               
genome at these two regions. Mutation at              
region 72 are considered to be the “L-type” and 
29 were classed “S-type”. S type is believed to 
be the ancestral strain descended from the 
animal and s type its human variant that 
developed later. S is wide spread in distribution 
Source:(https://www.newscientist.com/article/223
6544-coronavirus-are-there-two-strains-and-is-
one-more-deadly/#ixzz6HOHp3wF7)  

1.4 Recovery of the Novel, Corona Virus 
from the Feces 

 

Some researchers have reported the recovery of 
the virus from the feces, but its significance at 
present is not known. There is no evidence of 
feco-oral transmission. 
 

1.5 Reinfection 
 

The WHO has not yet confirmed any possibility 
of reinfection. 
 

1.6 Approaches to Corona Virus Vaccine 
Production 

 

1.6.1 Structure and antigens of corona virus 
 

The novel Corona virus is an enveloped virus 
containing a single stranded m RNA and a 
protein inside and spoke like projections of 
glycoprotein on the surface. The later earned the 
virus the name Corona, which means a crown. 
genome of SARS-CoV-2 (2019-nCoV) encodes 
the spike protein, the envelope protein, the 
membrane protein and the nucleocapsid protein. 
The spike protein (S-protein) mediates receptor 
binding and membrane fusion. Spike protein 
contains two subunits, S1 and S2. S1 contains a 
receptor binding domain (RBD), which is 
responsible for recognizing and binding with the 
cell surface receptor. S2 subunit is the "stem" of 
the structure, which contains other basic 
elements needed for the membrane fusion. The 
spike protein is the common target for 
neutralizing antibodies and vaccines.EuIs been 
reported that SARS-CoV-2 (2019-nCoV can 
infect the human respiratory epithelial cells 
through interaction with the human ACE2 
receptor. Indeed, the recombinant Spike protein 
can bind with recombinant ACE2 protein. It has 
been reported that SARS-CoV-2 (2019-nCoV) 
can infect the human respiratory epithelial cells 
through interaction with the human ACE2 
receptor. Indeed, the recombinant Spike protein 
can bind with recombinant ACE2 protein. The 
spike protein (s) on the envelope of the virus and 
m-RNA strand of the virus within the capsid are 
two novel approached in the vaccine industry 
(Source: Sino Biological, Inc with headquarters in 
Beijing, China with branches in the United States 
and Europe).  
 
1.6.2 The vaccine trials 
 
According to the Kaiser Permanente report “The 
artificial mRNA produced in the lab, prompts host  



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
64 

 

cells to build a protein found on the surface of the 
virus, . A person’s immune system would react to 
this new protein by building up an arsenal of 
antibodies that target and latch- onto this protein, 
tagging the virus for elimination. Then, the mRNA 
should break down and be eliminated by the 
body, leaving the vaccinated person better 
prepared to fight off SARS-CoV-2, if they are 
infected subsequently.  A clinical trial is slated on 
April 2020 to conduct a preliminary human safety 
clinical trial of this vaccine - a wall street journal 
reports. In February 2020, Novavax started 
testing its recombinant nanoparticle vaccine 
candidate for coronavirus in animal models. The 
candidates produced antigens derived from the 
coronavirus spike (S) protein. Novavax is 
planning to use its Matrix-M adjuvant with its 
Covid-19 vaccine candidates to boost immune 
responses. “CureVac has successfully 
harnessed its biological insights of the life-
enabling molecule mRNA to move medicine into 
the future. Powered by our optimization 
technology.” CureVac AG, a clinical stage 
biopharmaceutical company is pioneering 
mRNA-based vaccine against the novel corona 
virus. Recently The WHO approved hydroxy 
chloroquine vaccine for prophylaxis against 
Covid 19. WHO has published a long list of 
counties working on corona virus vaccine and 
their different approaches, in this regard. 
Interested can refer the same as it is out of the 
scope of this article.  
 

2. DISCUSSION  
 
It is proposed to briefly review the broad 
principles of immune reaction s to viral infections 
in general as the specific immune reaction of 
Corona virus 19 is to early to decipher. However, 
the intended focus is on the concept of Local 
immunity and it’s possible role in the 
interventional strategy to contain the disease. 
 
Principles of immune reactions against viral 
infections in general: There are two types of 
systemic immunity they are  
 

 Innate immunity 

 Adoptive immunity 
 

Innate and adoptive immune mechanisms both 
operate against the virus or the infected cells of 
the host. 
 
Cytotoxic cells: NK (Natural killer) and 
CD8+cells cytotoxic T cell circulate and kills cells 
that are infected with viruses with toxic 
mediators. Cytotoxic T cells have specialised 
proteins on their surface that help them to 
recognise virally-infected cells. These proteins 
are called T cell receptors (TCRs). Each 
cytotoxic T cell has a TCR that can specifically 
recognise a particular antigenic peptide bound to 
an MHC 1 molecule. The Virus have TCR 
receptors which express the viral proteins. The 
host cells have HLA 1 antigens to which the vral 
proteins are bound bind.  
 
NK cytotoxic cells are innate defence 
mechanisms which have fewer than normal MHC 
1 receptors on the surface of the cells. 
 
Toxic mediators of T cells: Preformed toxic 
mediators are stored called granules, in both 
cytotoxic T cells and NK cells, until contact with 
an infected cell triggers their release. 
 
One of these mediators is perforin, a protein that 
can make pores in cell membranes; these pores 
allow entry of other factors into a target cell to 
facilitate destruction of the cell.  
 
Enzymes called granzymes are also stored in, 
and released from, the granules. Granzymes 
enter target cells through the holes made by 
perforin. 
 
Once inside the target cell, they initiate a process 
known as programmed cell death or apoptosis, 
causing the target cell to die.  
 
Another released cytotoxic factor is granulysin, 
directly attacks the outer membrane of the 

Table 1. Showing the various viral immune mechanisms 
 

Immune mechanisms in viral infections 

 Against the infected cells Against the virus 

Innate NK Cells Interferons (a, b and g) 
Alternative compliment pathway  

Adaptive ADCC (Antibody dependant cell mediated 
cytotoxicity 

 

Classical complement pathway CD 8 Cytotoxic cells 
Phagocytosis  



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
65 

 

target cell, destroying it by lysis. Cytotoxic cells 
synthesise and release, cytokines, after making 
contact with infected cells. Cytokines include 
interferon-g and tumour necrosis factor-a. 
 
Interferon: It is one of the most effective innate 
defence mechanism produced by the infected. 
Host cell. There are 3 types of interferon, a, b 
and g the first two are mainly produced by 
monocytes-macrophages and to a lesser extent 
by fibroblasts. But interferon-g is produced by CD 
4 and CD 8 lymphocytes and NK cells. 
Mechanisms of Interferon action: "transitory 
resistance of cells; induction of different 
molecules with anti-viral activity; activation of 
genes expressing anti-viral proteins, and 
increasing the expression of SLA I and SLA II“.  
 
Role of Antibodies (Ig G, IgM,): 
 

1. Neutralisation of the virus (both IgG and 
IgM) 

2. Agglutination (IgM) 
 
Effectiveness of Humoral vs Cell mediated 
immunity (CMI): Some investigators have 
suggested that serum antibody is responsible for 
protection in the human, others have observed 
that influenza infection is not prevented by high 
levels of serum antibody Still investigators 
believe that serum antibody correlates with, but 
does not cause, protection. Cell-mediated 
immune responses are not only effective during 
acute phase of viral infection.when infected cells 
with virus are targeted by the CD 8+ subset of T 
cell population but also establish long-lived 
immunological memory by virtue of CD 4 + T 
cells.. These memory T cells become rapidly 
activated if they re-encounter virally infected cells 
and therefore function to protect against 
secondary exposures to the original viral 
pathogens. It can be host damaging if 
hypersensitive reaction develops as a part of 
immune reaction. It has also been proposed that 
cell-mediated immunity might be important in 
protection against viral infections as exemplified 
by the patients with hypogammaglobulinemia are 
not prone to more frequent or severe viral 
infections.  
 

2.1 The Concept of Local Immunity 
 
Historical perspective of the concept of local 
immunity [5]: Prof Besredka is the founder of 
this type of immunity. Working in Pasture institute 
in 1924, he developed his concept and tested on 
different organisms. He showed that B anthracite 

inoculated intraperitonially in guinea pig neither 
produced antibodies in the blood nor protected 
the animal from subsequent challenge with the 
live virus. age also proved that the organism 
when applied to the skin, though it did not also 
develop any antibodies, protected the animal 
from subsequent challenge with the 
microorganism. This study has driven home two 
truths. One, that immunity against the infection 
can be achieved even in the absence of raising 
antibodies against it. Second, vaccinating the site 
which is the portal of entry of the micro organism 
conferred immunity, independent of humoral 
immunity. This type of immunity, he called as 
"Local immunity". 
 

2.2 Review of Some of the Diseases to 
Which the Concept of Local Immunity 
is Applied and Tested 

 
2.2.1 Local immunity in polio virus infection 

[6] 
 
The Salk polio vaccine, which consists of killed 
virus administered systemically, elicits serum IgG 
as the major antibody and induces little or no 
secretory response. As a result, the immunized 
individual resists systemic infection, but may 
become a temporary carrier, with virus persisting 
at the intestinal portal of entry because of the 
lack of secretory antibody. The orally 
administered, live Sabin polio vaccine, on the 
other hand, induces secretory antibody in the 
intestine and is effective in preventing replication 
and subsequent mucosal penetration by the 
virus. However US stopped OPV in favour of IPV 
(inactivated polio vaccine) to prevent resurgence 
of type 2 polio virus.  
 
2.2.2 Local immunity in the influenza virus 

infection 
 

Influenza infection of the ferret resembles the 
disease in the human, [7] and has been studied 
extensively by HENRY BARBER and PARKER 
A. SMALL, JR, who showed that influenza 
infection in the ferret is a local phenomenon, 
whereas recovery from active infection is 
influenced by systemic immune mechanism" [8]. 
Several workers [9,10,11] have shown that 
natural infection with respiratory viruses 
stimulates the production of immunoglobulin A 
antibodies in secretions and leads to resistance 
to reinfection, it has been postulated that a 
vaccine’s ability to stimulate nasal secretary 
antibody is the deciding factor in protection of 
humans against influenza infection, and some 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
66 

 

field trials of local immunization gave promising 
results. [12,13,14,15]. On the contrary, trial of 
local immunization [16] as well as attempts to 
correlate secretary immunoglobulin A antibody 
with protection [17] was unsuccessful. The study 
suggested that srum antibody was irrelevant to 
prevention of influenza and recovery from 
influenza in the ferret [18]. Antibodies directed to 
the 2 major viral surface membrane proteins, 
hemagglutinin (HA) and neuraminidase (NA), 
mediate protection against reinfection following 
natural infection or vaccination. Some 
investigators have suggested that serum 
antibody is responsible for protection in the 
human, [19] others have observed that influenza 
infection is not prevented by high levels of serum 
antibody [20]. Several investigators believe that 
serum antibody correlates with, but does not 
cause, protection [21]. The lack of virus 
dissemination is consistent with the inability to 
detect viremia during influenza infection of ferrets 
and humans [22].  
 
Mucosal immunity in Shigella et al. [23] explored 
the mechanisms of protection mediated by 
Shigella LPS-specific secretory IgA (SIgA), the 
major mucosal Ab (antibody) induced upon 
natural infection. They found that anti-Shigella 
LPS SIgA, mainly via immune exclusion, 
prevented Shigella-induced inflammation 
responsible for the destruction of the intestinal 
barrier. In the form of immune complexes, SIgA 
guarantees both immune exclusion and 
neutralization of translocated bacteria, thus 
preserving the intestinal barrier integrity by 
preventing bacterial-induced inflammation. These 
findings add to the multiple facets of the non- 
inflammatory properties of SIgA. 
 

2.2.3 Mucosal immunity in infection by                  
V. cholerae [24] 

 

Bloom PD, et al. reviewing the mucosal immunity 
against enteric bacterial pathogens states that "V 
cholerae, secretes cholera toxin (CT), a potent 
enterotoxin that induces a voluminous diarrhea 
via adenylate cyclase-dependent chloride 
secretion. Protective immunity is based on 
secretory (s) immunoglobulin A directed against 
whole-cell components that prevent attachment 
to gut epithelial cells and is enhanced by CT, an 
immunogen with potent adjuvant activity".  
 

Mycoplasma and local immunity: Lisa M. 
Hodge, Jerry W. Simecka et al. [25] in their study 
concluded that "local immunity along the 
respiratory tract plays a major role in resisting 
and controlling mycoplasma infection and should 

be considered in vaccine development against 
mycoplasma respiratory diseases. Generation of 
immunity in the upper respiratory tract appears to 
be optimal in preventing the initial mycoplasma 
infection at this site, but adjuvants (like cholera 
toxin (CT) enhanced these protective responses. 
In the lower respiratory tract, pulmonary immune 
responses seem to be more effective than serum 
antibody responses and nasal immunization can 
confer some protection from pulmonary 
infection".  
 

Role of the secretary IgA in local immunity 
[26]: Secretory IgA (SIgA) is the principal 
immunoglobulin (Ig) on mucosal surfaces of 
humans the respiratory contains equivalent 
amounts of IgA and IgG in addition to some IgM 
(Brandtzaeg et al., 1999). The main function of 
IgA is the neutralization of pathogens and toxins 
without causing inflammation since it does not 
activate complement (Cerutti, 2008; Macpherson 
& Slack, 2007). 
 

The mucosal microbiota, epithelial cells, and the 
mucosal immune system constitute a stable and 
interdependent “tripod” that maintains mucosal 
homeostasis by complex mechanisms (Corthesy, 
2007; Hooper, 2004).  
 

1. Bacteria adhere to the surface receptors of 
the epithelial cells and express the 
basolateral membrane receptor (polymeric 
Ig receptor; pIgR) that transports locally 
produced polymeric (p)IgA into the external 
secretions (Kaetzel & Mostov, 2005).  

2. Endogenous bacterial of the intestinal 
tract, and the respiratory and genital tracts, 
are coated in vivo with SIgA (Bos, Cebra, 
& Kroese, 2000; van der Waaij et al. 2004) 
that limits their epithelial adherence and 
penetration, thereby confining them to the 
mucosal surfaces. 

 

IgA neutralizes inflammatory microbial products 
inside epithelial cells (Fernandez et al., 2003). 
Finally, if bacteria trespass the epithelial barrier, 
IgA transports these bacteria back into the lumen 
via pIgR or promotes their phagocytosis through 
Fc (Pasquier et al., 2005; Phalipon Corthésy, 
2003). 
 

Killed bacteria seem to be at least 100-fold less 
effective at inducing IgA responses than live 
bacteria, presumably due to their inactivity and 
the digestion of dead bacteria during                    
transit through the stomach and intestine 
(Hapfelmeier et al. 2010; Macpherson & Uhr, 
2004). 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
67 

 

2.2.4 Concept on local immunity as applied 
to in covid 19 immunity 

 
2.2.4.1 Recapitulation of some considerations 
 

1.  Belyakov et al. [27] opined that: 
 

A. "The route of vaccination is important in 
influencing immune responses at the 
initial site of pathogen invasion where 
protection is most effective. Immune 
responses required for mucosal 
protection can differ vastly depending on 
the individual pathogen. For some 
mucosal pathogens, high-titer 
neutralizing antibodies (Abs) that enter 
tissue parenchyma or transude into the 
mucosal lumen are sufficient for clearing 
cells, free of the virus." 

B. Induction of the mucosal innate and 
adaptive immune systems, including 
CD4+ T helper cells, Th17, high avidity 
CD8+ CTL and secretory IgA and IgG1 
neutralizing Abs, at the site of pathogen 
entry may be required for effective 
protection against highly invasive 
pathogens. 

 

2.  The main function of the innate mucosal 
immune system, to discriminate between 
dangerous and innocuous organisms, is 
determined by the recognition of specific 
pathogen-associated molecular patterns 
via activation of TLRs, NOD-like receptors, 
retinoic acid (RA)-inducible gene I-like 
helicases, and C-type lectins [28]. 

3.  Studies evaluating mucosal infection and 
immunization in humans and animals have 
demonstrated the existence of a common 
mucosal immune system (CMIS) that 
consists of gastrointestinal, respiratory, 
and genital mucosa [29]. 

4.  The CMIS implies the ability of Ag-specific 
lymphocytes to home to mucosal effector 
sites in addition to the site where initial Ag 
exposure occurred [30] compartmentalized 
mucosal immune responses (CMIRs) that 
consist of innate responses, mucosal Abs 
(secretory Ig (sIg) A and sIgG) and CD8+ 
CTLs localized to tissues proximal to the 
mucosal site of immunization are 
necessary for protection from mucosal 
pathogens (Belyakov et al.). 

5.  Protective immunity against mucosal 
pathogens will require novel vaccine 
strategies to induce mucosal immune 
responses tailored to the anatomic location 
and the threat of the invading pathogen 

6.  Protective immunity against mucosal 
pathogens will require novel vaccine 
strategies to induce mucosal immune 
responses tailored to the anatomic location 
and the threat of the invading pathogen 
pathogens may require mucosal vaccine 
strategies that activate multiple arms of the 
innate and adaptive immune systems 
[31,32,33,34,35]. 

7.  Optimum mucosal vaccination leading to 
compartmentalized mucosal immune 
responses might ensure that the 
appropriate cells are armed and ready to 
respond immediately to infection and to 
confer protection not achieved following 
natural infection. 

8.  Protective mucosal immune responses are 
most effectively induced by mucosal 
immunization through oral, intranasal (i.n.), 
intrarectal, or intravaginal routes, and an 
optimized mucosal vaccination strategy 
may have a much greater potential for 
generating local protective mucosal 
immune responses.  

9.  Mucosal immunity concept has worked 
well in case of viral infections like 
influenza, poliomyelitis and bacterial 
infections like salmonella and V. cholerae 
and mycoplasma infections, as outlined 
above.  

10. The CDC has not made any comments 
regarding the relative merits of the 
inactivated and recombinant vaccine and 
nasal spray vaccine for influenza. 

 
The proposed hypothesis: Covid 19 is different 
from other deadly viral infections, say for 
instance HIV. In the later, the virus is found in all 
body secretions including semen with variable 
infectivity of each body fluid. There is no 
suggestion of any tissue "tropism" in HIV. As 
against HIV, the corona virus (CoV) enters the 
body through the nose, multiplies there, and 
excreted through nasal secretion. In fact, they 
are limited almost exclusively in the upper 
respiratory epithelium initially and later if not 
prevented, spreads locally to lower respiratory 
epithelium, suggesting some sort of "tissue 
tropism". Additionally, the novel corona virus is 
shown not to be disseminated beyond the 
respiratory tract. The recent reports of 
involvement of cardiovascular system 
(myocarditis) and a couple of cases of 
involvement of the brain, have no proof of direct 
involvement of the cov, beyond reasonable 
doubt. It could’ve be due to fallout of the immune 
reactio mounted against the virus. Consequently 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
68 

 

the cause of high mortality associated with Covid 
19, is restricted to a deadly type of pneumonia. If 
the infection could be arrested at portal of entry, 
i.e. the nasal epithelial level, the disastrous 
consequences of spread to lower respiratory 
tract; ĺmay be averted. This makes a strong case 
for creating local immunity at the level of the 
nasal epithelium itself. Local mucosal infections 
of the respiratory or gastro-intestinal tract may 
elicit local cell-mediateld and humoral (IgA) 
immune responses, but not necessarily systemic 
immunity. Conversely, systemic immunity does 
not always lead to local mucosal immunity. 
localized infections of mucosal surfaces, and the 
protection derived , does not correlate with the 
presence of serum antibody, but it does correlate 
with the presence of local IgA antibody, as has 
been shown in human studies of viruses 
restricted to the respiratory tract (e.g., respiratory 
syncytial virus and influenza virus) or to the 
gastrointestinal tract (e.g., enteroviruses).  
 

The route of administering the vaccine is the 
major determinant of the issue immunity. The 
past experience of intranasal vaccine as is 
approved for influenza may be taken as an 
example, in the case of Covid 19. It is also 
shown that prior systemic vaccination may 
interfere with the recall memory exercised by the 
nasal mucosa, should the pathogen cause 
reinfection the same person. There is no 
permanent infection-induced immunity conferred 
by the Covid 19. This factor also supports the 
suggestion of raising local immunity of nasal 
epithelium by administering the vaccine 
intranasally. It is logical that raising local 
immunity in nasal epithelium may give a multi- 
pronged protection from the Covid 19. against 
entry multiplication. As well excretion in nasal 
sections. The last one is very important from 
public health point of view , in preventing the 
spread of the infection to others. Local immunity 
is found to be effective at least in two diseases. 
To elaborate this point, the polio virus, whose 
portal of entry of the infection is the gastro-
intestinal tract, oral polio vaccine is the time 
tested vaccine that conferred immunity to polio 
virus. It is shown to be effective by raising 
mucosa immunity both at pharyngeal and 
intestinal levelled –IPV (inactivated polio vaccine) 
was less effective than OPV in preventing and 
limiting intestinal infection, even though it 
induced higher post vaccination serum antibody 
levels. While opv (oral polio vaccine) checks the 
excretion of polio virus through faeces (there by 
preventing the spread of infection to others, [36] 
the continued excretion of the polio virus in case 
of immunisation by the inactivated vaccine 

administered by parenteral route, poses risk of 
continued deco-oral transmission, though it 
offered immunity at the personal level. Secondly, 
the influenza vaccine administered intranasally 
as a spray type vaccine has been accepted 
efficacy-wise by the CDC. 
 

3. CONCLUSION  
 

The COVID 19, as seen from the tropism to 
airway (nasal) epithelium through which it gains 
entry, multiplies and even shed in the nasal 
secretions, indicates that, efforts to raise the 
local immunity of the respiratory epithelium, 
especially at the very portal of its entry, may be 
fruitful in ‘nipping the infection in the bud’. 
Accordingly in the case of Covid 19, vaccine 
developed might be effective, if administered 
intranasally, rather than other routes of vaccine 
administration, it is felt. 
 

CONSENT AND ETHICAL APPROVAL 
 

It is not applicable. 
 

COMPETING INTERESTS 
 

Author has declared that no competing interests 
exist. 
 

REFERENCES  
 
1. Zhang S, Na J, Zhou W, Liu B, Yang W, 

Zhou P, et al. A familial cluster of COVID-
19 indicating virus can be transmitted by 
asymptomatic carriers. [Submitted]. Bull 
World  
Health Organ. E-pub; 2020.  

2. Yan Bai, Lingsheng Yao, Tao Wei,                      
et al. Presumed asymptomatic carrier 
transmission of COVID-19. JAMA;                 
2020. 

3. Camilla Rothe, Mirjam Schunk, Peter 
Sothmann, et al. Transmission of 2019-
nCoV infection from an asymptomatic 
contact in Germany, NEJM; 2019.  
DOI: 10.1056/NEJMc2001468 

4. Study claiming new coronavirus can be 
transmitted by people without symptoms 
was flawed. Local Immunity in Infectious 
Diseases. Nature. 2020;113:242–243. 
Available:sciencemag.org/news/2020 

5. Aford RH, Rossen RD, Butler WT, Kasel 
JA. Neutralizing and hemagglutination i 
nhibiting activity of nasal secretions 
following experimental human infection 
with A2 influenza virus. J. Mmunol. 
1967;98:724-731. 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
69 

 

6. Welliver RC, et al. Importance of local 
immunity in enteric infection. Review 
Article. J Am Vet. MedAssoc; 1978. 

7. Potter CW, Oxford JS, Shore SL, McLaren 
C, Stuart-Harris CH. Immunity to influenza 
in ferrets. I. Response to live and killed 
virus. Br. J. Exp. Pathol. 1972;53:153-167. 

8. Henry Barber W, Parker A, Small JR. Local 
and systemic immunity to influenza 
infections in ferret. Infection and Immunity. 
1978;221-2283. 

9. Aford RH, Rossen RD, Butler WT, Kasel 
JA. Neutralizing and hemagglutination 
inhibiting activity of nasal secretions 
following experimental human infection 
with A2 influenza virus. J. Immunol. 
1967;98:724-731. 

10. Rossen RD, Douglas RG, Cate TR, Couch 
RB, Butler WT. The sedimentation 
behaviour of rhino virus neutralizing activity 
in nasal secretions and serum following the 
rhinovirus common cold. J. Immunol. 
1966;97:532-538. 

11. Smith CB, Purcell RH, Bellanti JA, 
Chanock RM. Protective antibody to para 
influenza type 1 virus. N. Engl. J. Med. 
1966;275:1145-1152.  

12. Liem KS, Jacobs J, Marcus EA, Van Strik 
R. The protective effect of intranasal immu; 
1973. 

13. Waldman RH, Coggins WJ. Influenza 
immunization: Field trial on a university 
campus. J. Infect. Dis. 1972;126:242-248. 

14. Waldman RH, Mann JJ, Small PA, Jr. 
Immunization against influenza: prevention 
ofillness in man by aerosolized inactivated 
vaccine. J. Am. Med. Assoc. 
1969;207:520-524. 

15. Barber WH, Small PA, Jr. Construction of 
an improved tracheal pouch in the ferret. 
Am. Rev. Respir. Dis. 1976;115:165-169. 

16. Edmondson WP, Jr. Rothenberg R, White 
PW, Gwaltney JM, Jr. A comparison of 
sub-cutaneous, nasal and combined 
influenza vaccination; 1971. 

17. Downie JC, Stuart-Harris CH. 
Theproduction of neutralizing activity in 
serum and nasalsecretion following 
immunization with influenza B. vi-rus. J. 
Hyg. (Cambridge). 1970;68: 233-244. 

18. Small PA Jr., Waldman RH, Bruno JC, G. 
Gifford E. Influenza infection in ferrets: 
Role of serum antibody in protection and 
recovery. Infect. Im-mun. 1976;13:417-
424. 

19. Stuart-Harris C. Influenza-the problems 
and the, future. Med. J. Small PA, Jr. 

Waldman RH, Bruno JC, Gifford GE. 
Influenza infection in ferrets: role of serum 
antibody in protection and recovery. Infect. 
Im-mun. 1973;13:417-424. 

20. Morris JA, Kosel JA, Saclam M, Knight V, 
Loda FA. Immunity to influenza as related 
to antibody levels. N. Engl. J. Med. 
1966;274:527-535. 

21. Kaji J, Oseasohn R, Jordan WS, Dingle 
JH. Isolation of Asian virus from 
eztrapulmonary tis-sues in fatal human 
influenza. Proc. Soc. Ezp. Biol. Med. 
1959;100:272-275. 

22. Kilbourne ED, Butler WT, Rossen RD. 
vibrio ref. 

23. Bloom PD, et al. Mucosal immune 
responses to intestinal bacterial 
pathogens. Semin Gastrointest Dis; 1996. 

24. Boullier S, et al. Secretory IgA-mediated 
neutralization of Shigella flexneri prevents 
intestinal tissue destruction by down-
regulating inflammatory circuits. J 
Immunol; 2009. 

25. Lisa M. Hodge, Jerry W. Simecka Role of 
upper and lower respiratory tract immunity 
in resistance to mycoplasma respiratory 
disease. The Journal of Infectious 
Diseases. 2002;186 (2)290–294. 

26. Robert Herich. Is the role of IgA in local 
immunity completely known?, Food and 
Agricultural Immunology. 2017;28(2):223-
237.  
DOI: 10.1080/09540105.2016.1258547  

27. Belyakov IM, Hel Z, Kelsall B, Kuznetsov 
VA, Ahlers JD, Nacsa J, Watkins DI, Allen 
TM, Sette A, Altman J, et al. Mucosal AIDS 
vaccine reduces disease and viral load in 
gut reservoir and blood after mucosal 
infection of macaques. Nat. Med. 
2001;7:1320–1326. 

28. Ichinohe T, Lee HK, Ogura Y, Flavell R, 
Iwasaki A. Inflammasome recognition of 
influenza virus is essential for adaptive 
immune responses. J. Exp. Med. 
2009;206:79–87. 

29. Kantele A, Ha¨kkinen M, Moldoveanu Z, Lu 
A, Savilahti E, Alvarez RD, Michalek S, 
Mestecky J. Differences in immune 
responses induced by oral and rectal 
immunizations with Salmonella typhi 
Ty21a: Evidence for compartmental-ization 
within the common mucosal immune 
system in humans. Infect. Immun. 
1998;66:5630–5635. 

30. Bienenstock J, Befus AD, McDermott M, 
Mirski S, Rosenthal K, Tagliabue A. The 
mucosal immunological network: 



 
 
 
 

Prasad; AJI, 3(1): 61-70, 2020; Article no.AJI.55881 
 
 

 
70 

 

Compartmentalization of lymphocytes, 
natural killer cells and mast cells. Ann. NY 
Acad. Sci. 1983;409:164–170. 

31. Wang J, Thorson L, Stokes RW, 
Santosuosso M, Huygen K, Zganiacz A, 
Hitt M, Xing Z. Single mucosal, but not 
parenteral, immunization with recombinant 
adenoviral-based vaccine provides potent 
protection from pulmonary tuberculosis. J. 
Immunol. 2004;173:6357–6365. 

32. Neutra MR, Kozlowski PA. M30. Neutra 
MR, Kozlowski PA. Mucosal vaccines: the 
promise and thechallenge. Nat. Rev. 
Immunol. 2006;6:148–158. 

33. Gallichan WS, Rosenthal KL. Long-lived 
cytotoxic T lymphocytememory in mucosal 
tissues after mucosal but not systemic 
immunization. J. Exp. Med. 1996;184:1879 
–1890. 

34. Revaz V, Benyacoub J, Kast WM, Schiller 
JT, De Grandi P, Nardelli-Haefliger D. 

Mucosal vaccination with a recombinant 
Salmonella ty-phimurium expressing 
human papillomavirus type 16 (HPV16)               
L1 virus-like particles (VLPs) or                  
HPV16 VLPs purified from insect cells 
inhibits the growth of HPV16-expressing 
tumor cells in mice. Virology. 2001;279: 
354–360. 

35. Kozlowski PA, Cu-Uvin S, Neutra MR, T. 
Flanigan P. Comparisonof the oral, rectal 
and vaginal immunization routes for 
induction of antibodies inrectal and genital 
tract secretions of women. Infect. Immun. 
1997;65:1387–1394. 

36. Majid Laassri, Kathleen Lottenbach, 
Robert Belshe, Mark Wolff, Margaret 
Rennels, Stanley Plotkin, Konstantin 
Chumakov. Effect of different vaccination 
schedules on excretion of oral poliovirus 
vaccine strains. The journal of Infectious 
Diseases. 2005;192(12):2092–2098. 

_________________________________________________________________________________ 
© 2020 Prasad; This is an Open Access article distributed under the terms of the Creative Commons Attribution License 
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, 
provided the original work is properly cited. 
 
 

 

 

 

 

 

  

Peer-review history: 
The peer review history for this paper can be accessed here: 

http://www.sdiarticle4.com/review-history/55881 

http://creativecommons.org/licenses/by/4.0

