Introduction to vacciniology

Department of Community Medicine, Grant Medical College ,Mumbai

1

College seminar schedule for month of July 2015

Sr.No.

Date Name Of PG student Topic PG Teachers

1 02/07/2015 Dr. Santosh Kadle Introduction to Vaccinology

Dr. Lalit Sankhe

Dr. Amit Mohite2 09/07/2015 Dr. Vinod Chaudhary Cold Chain Management

3 16/07/2015 Dr. Amol Askar National Immunization programme

4 23/07/2015 Dr.Deepanjali Gadgikar Reporting of AEFI

5 30/07/2015 Dr. Santosh Kadle Future Generation Vaccines

16/07/2015


2

Discussion Schedule for month of July 2015 Sr.No.

DateImmunization Module

Topic PG student PG teachers

1 03/07/15 I II

IntroductionVaccine preventable disease & Surveillance Of VPD

Dr . Upadhye Dr . Dange

Dr. Lalit Sankhe

Dr. Amit Mohite

2 10/07/15 III IV

Manage cold chain Plan and implement immunization services

Dr . Pisharodhi Dr . Kale

3 17/07/15 V VI

Adverse events following immunization (AEFI)Special programme for vaccine preventable disease

Dr . Satpathy Dr . Aatram

424/07/15

VII Monitor and evaluate immunization services Vaccine manufacturing & Trial

Dr . Panigrahi Dr . Nishant

5 31/07/15

Adult vaccination Dr . Sid

16/07/2015


3

Introduction To Vaccinology PG Student : Dr.Santosh Kadle PG Teachers: Dr. Lalit Sankhe

Dr. Amit Mohite

16/07/2015


4

Contents of seminar : Vaccinology Achievements Global immunization vision and strategy (GIVS) goals Need of Vaccines Basic Concept of Immunity Development of vaccine/200 years of revolution Type of Vaccines Vaccines currently in use Major milestones in vaccine developments and licensing in India List of licensed vaccine manufacturing units in India Year of start of vaccine manufacturing units in India Issues of vaccine- efficacy , immunogenicity and safety Global monitoring of vaccine Monitoring of vaccine in India Criteria for selection of vaccines for introduction in NIP

16/07/2015


5

Vaccinology

• The branch of medicine concerned with the development of vaccines.

• The word vaccine comes from Latin word “Vaccinus”- pertaining to cows

• Vaccine is “an immuno-biological substance designed to produce specific protection against a given disease.” It stimulates the production of protective antibodies and other immune mechanisms.

16/07/2015

http://www.oxforddictionaries.com/definition/american_english/medicine#medicine__5

http://www.oxforddictionaries.com/definition/american_english/vaccine#vaccine__2


6

What’s so special about vaccines? -- Vaccines are special !!!

Unlike many other health intervention, they help healthy people stay healthy & in doing to help to remove a major obstacle to human development.

They benefit not only individual but also communities & even entire population(e.g. eradication of small pox , elimination of poliomyelitis)

Impact of vaccine on communities &population are more rapid than that of many other health intervention.

United state –CDC (Centre for disease control & prevention) put vaccine on top of list of Ten great public health achievements of 20 th century.

Copenhagen Census Center in 2008 put expanded coverage for children in fourth Place on List of 30 cost effective ways of advancing Global welfare.

16/07/2015


7

• Immunization is key to achieving the Millennium Development Goals (MDGs),especially the goal to reduce deaths among children under five years old (MDG 4).

• Vaccines prevent more than 2.5 million child deaths a year.

• Available vaccines could prevent additional 2 million deaths a year among children under five years old.

• The introduction of new vaccines against pneumococcal disease and rotavirus could have a rapid impact-within 3 to 5 years – on reducing the high toll of sickness , disability, and deaths among children under five years old.

• Over 100 million children are immunized every year before their first birthday.

• But still issue is--around 24 million children under one year old - almost 20% of the children born every year- are not being reached with vaccines.

16/07/2015


8

Global immunization vision and strategy (GIVS) goals By 2010 or earlier: Increase coverage. Countries will reach at least 90% national vaccination

coverage and at least 80% vaccination coverage in every district.

Reduce measles mortality: Globally, mortality due to measles will have been reduced by 90% compared to the 2000 level.

16/07/2015


9

Global immunization vision and strategy (GIVS) goals

By 2015 or earlier: Sustain coverage. vaccination coverage goal reached in 2010 will have been

sustained. Reduce morbidity and mortality- of vaccine preventable diseases by at least

2/3 of the 2000 level Ensure access to vaccines of assured quality Introduce new vaccines Ensure capacity for surveillance and monitoring Strengthen systems Assure sustainability

16/07/2015


10

Why we need vaccines?

• The control of infection is approached from several directions.

• One method of breaking the chain of infection –e.g. in UK , rabies and psittacosis control by controlling the importation of dogs and parrots respectively.

• Improvements in public health-water supply , sewage systems , and education in personal hygiene- prevent the spread of cholera and many more diseases.

• And off course when other measures fail we can back on induction of immunity.

16/07/2015


11

What is immunity ?• Immunity is “ a state of being exemption from penalty ,duty , obligation , injury or

harmful influences.”

• Word -Immunity comes from Latin word – “Immunitos” -exemption from civic duties afforded to senators, exemption from military services/tax.

• Immunity is basically constitutes of recognition mechanism and self/non-self mechanism.

• Its of two types- 1]Natural /Innate immunity 2] Acquired/ adaptive immunity

16/07/2015


12

Active immunity - It is the immunity which an individual develops as a result of infection or by specific immunization and is usually associated with presence of antibodies or cells having a specific action on the microorganism concerned with a particular infectious disease or on its toxin.• In other words , active immunity depends upon the humoral and cellular responses of the host.• The immunity produced is specific for a particular disease.• Active immunity may be acquired in 3 ways: a) following clinical infection, e.g. chicken pox, rubella &measles b) following subclinical or in apparent infection, e.g. polio & diphtheria c) following immunization with an antigen which may be a killed vaccine , a live attenuated vaccine or toxoid

16/07/2015


13

Natural immunity is nonspecific, no change with repeat exposure.While Acquired immunity is specific and memory against exposure.

Humoral immunity Cell mediated immunity

B lymphocyte T-lymphocyte

--Responds to antigen by differentiating into antibody producing plasma cells. --Effective against extracellular pathogens and their products. -- Antibodies binds their structure and cause their destructions.

--Effective against intracellular pathogens(like viruses , bacteria , parasite)--Elimination of intracellular pathogen by causing the lysis of infected cells and intracellular destruction of microorganism.

16/07/2015


14

Passive immunity -- When antibodies produced in one body(human or animal) are transferred to another to induce protection against disease, it is known as passive immunity. In other words, the body does not produce its own antibodies but depends upon ready- made antibodies. Passive immunity may be induced : a) by transfer of maternal antibodies across the placenta .Human milk also contains protective antibodies,(IgA) b) by administration of an antibody- containing preparation(immune globulin or antiserum) Passive immunity differs from active immunity in following respects- 1)immunity rapidly established, 2)immunity produced is only temporary till antibody is eliminated from body and 3)there is no education of the reticuloendothelial system.

16/07/2015


15

Herd immunity - It is a type of immunity that occurs when the vaccination of a portion of population (or herd) provides protection to unprotected individuals. Herd immunity provides an immunological barrier to the spread of disease in the human herd.

16/07/2015


1616/07/2015


17

Types of Vaccines

• Approaches to designing vaccines against a microbe are typically based on fundamental information about microbe such as how it infects cells and how the immune system responds to it, as well as practical considerations.

• Following are types of vaccine depending upon their content and preparation method :

1] Live, attenuated vaccines 2] Inactivated vaccines 3] Subunit vaccines 4] Combination

16/07/2015


1] Live Attenuated Vaccine:• Live vaccines(e.g. BCG ,OPV , Measles) are prepared from live or wild organism.• These organisms have been passed repeatedly in laboratory in tissue culture or chick embryos

and have their capacity to induce full-blown disease but their immunogenicity is there.• Live vaccines are more potent immunizing agent than killed vaccines , because : 1] Live organism multiply in the host and resulting antigenic dose is larger than what is injected. 2] Live vaccines have all the major and minor antigenic components. 3] Live vaccines engages certain tissues of body ( e.g. intestinal mucosa by OPV) 4] There may be the other mechanisms such as the persistence of latent virus.• Live vaccines should not be administered to persons with immune deficiency diseases or whose

immune response may be suppressed because of leukaemia ,lymphoma ,malignancy or therapy with steroids , anticancer drugs or radiation .

• Pregnancy is another contraindication unless the risk of infection exceeds the risk of harm to foetus.

• When two live vaccines are required they should be given either simultaneously at different site or with interval of at least 3 -4 weeks apart.

16/07/2015 18


19

• Protection is generally achieved with single dose of vaccine.• An additional dose is given to ensure the seroconversion. (e.g. with single dose of measles

there is response up to 95-98%, but the second dose ensures 100% s protection against measles)• Live vaccines usually produce durable immunity, but not always as long as that of natural

infection.• Live vaccines must be properly stored to retain effectiveness. Serious failure of measles and

polio immunization have resulted from inadequate refrigeration prior to use .

16/07/2015


20

2] lnactivated Vaccine:• Inactivated vaccines are produced by growing virus or bacteria in culture media and

then inactivating them with heat and chemicals (usually formalin),when injected in body they stimulate active immunity.• They are usually safe but less efficacious than live vaccines.(e.g. cholera vaccine offer

50% protection while efficacy of pertussis vaccine is 80% in first three years and almost NIL in 12 years after immunization.• Killed vaccines require a primary series of 2 to 3 dose of vaccine to produce an

adequate antibody response and in most cases booster are required.• The duration of immunity following the use of inactivated vaccines varies from months

to many years.• A vaccine is inactivated , the infective agent can not grown in immunized so that it can

not cause the disease , even in an immunodeficient person.• The only absolute contraindication is a severe local or general reaction to a previous

dose.16/07/2015


21

• Unlike live antigen, inactivated antigens are not affected by circulating antibody.

• They need adjuvant for action and preparation

• Inactivated vaccines are often more stable than attenuated vaccines. So they have very high stability at room temperature.

16/07/2015


22

3] Subunit Vaccine:• A vaccine can be made of single or multiple antigenic components of a microorganism that

are capable of stimulating a specific immune response sufficient to protect from the relevant pathogen infection or from the clinical manifestation of the disease.• Depending on the molecular composition of the purified antigen used to prepare the vaccine

and on the techniques applied to obtain the final material used as a vaccine , different types of subunit vaccines can be defined.

• Types of subunit vaccines : 1] Toxoid 2] Protein Vaccine 3] Recombinant protein vaccine 4] Polysaccharide based vaccine 5] Conjugated vaccine

16/07/2015


23

1] Toxoid vaccine

• Certain organisms produce exotoxins,( e.g. diphtheria and tetanus bacilli ).

• The toxins produced by these organisms are detoxicated and used in the preparation of vaccines.

• The antibodies produced neutralize the toxic moiety produced during infection, rather than act upon the organisms.

• In general , toxoid preparations are highly efficacious and safe immunizing agents.

16/07/2015


24

2] Protein vaccine

• single or multiple protein from pathogen used for protein vaccine.

• Purification of protein in vitro culture done before used in the preparation of vaccines.• Example – 1] Acellular pertussis vaccine is prepared from 2-4 different purified protein from B.Pertusis , which is more effective than vaccine from whole organism 2] Influenza subunit prepared from Haem-agglutinin (HA) & Neuro-aminodase (NA) and purified from inactivated infective virus

16/07/2015


25

3] Recombinant protein (DNA) Vaccine• Development of recombinant deoxyribonucleic acid (DNA) technology has made

possible the expression of protective protein antigen in heterologous expression systems such as E.coli, yeast, mammalian cells, or baculovirus.• This technology avoids the problems related to growing and manipulating large amounts of a pathogen from which the antigen is purified.• As in this ,better purified protein antigen is used, more cleaner vaccine preparation is there. But this causes decrease in immunogenicity , so need of adjuvants to enhance immunogenicity.• Example – 1] Hepatitis vaccine is prepared by inserting segments of Hepatitis B gene into yeast cell and then modified yeast cell used for preparation of vaccine. As recombinant Hepatitis B vaccine not contain virus DNA ,it is unable to produce infection.

16/07/2015


26

4] Polysaccharide based vaccine

• In some bacteria, there is capsular shell of bacteria which constitutes polymeric glycan and which is act as shield or barrier against host immune response.• Stimulation of antibody response against this surface polysaccharides of pathogenic bacteria is main strategy for preparation of vaccine.• Disadvantage- as chemical structure of surface polysaccharides varies with species

and strains , vaccine is to serotype specific.• Example – 1] Hib vaccine 2] Pneumococcus 3] Typh.(Vi) 4] Meningococcus

16/07/2015


27

5] Conjugate Vaccine

• Children under two years of age do not respond well to antigens, such as polysaccharides , which produce antibodies via a t –cell independent mechanism.

• Polysaccharide antigen are chemically linked(conjugated) to a protein that T–cells recognize, then these conjugate vaccines can elicit strong immune responses and immune memory in young children.

• The conjugate vaccines are also sero-type specific , and ,therefore, multivalent formulations are required to achieve protection against multiple serotypes.

• Examples are S.pneumococcal and meningococcal vaccines.

16/07/2015


28

4] Combination vaccines:

• In this, more than one kind of immunizing agent used for vaccine preparation.• Basic aim for this vaccine preparation are- simplify administration , decrease in cost , decrease in no . of frequency, decrease in storage cost and facilitation of new addition of vaccines in national immunization programme.• Example – 1] DPT 2] DT 3] DP 4]DPT a 5]MMR 6]Hepatitis A ,B 7] DTwp 8] DPT , Hep B , Hib

16/07/2015


29

Vaccines currently in useLive attenuated Killed organism Toxoid/protein Polysaccharide Glyco-conjugate Recombinant

• BCG • Typhoid • Diphtheria Pneumococcus Hib HBV

• Yellow fever • Cholera • Tetanus meningococcus Pneumococcus Lyme disease

• Polio (OPV) • Plague • Acellular Pertussis Hib MenACWY Cholera Toxin B

• Measles • Pertussis • Anthrax Typhoid (Vi) HPV

• Mumps • Influenza • Influenza subunit

• Rubella • Typhus

• Typhoid • Polio (IPV)

• Varicella • Rabies

• Rotavirus • JE

• Cholera • TBE

• Cold adapted influenza

• HAV

• Rotavirus reassortants

• Zoster

16/07/2015


30

Major milestones in vaccine developments and licensing in India

1893- Efficacy trails on cholera vaccine conducted in Agra , India

1897- First plague vaccine discovered by Dr.Haffkine1904-05 first vaccine research institute established at Kasauli , Himachal Pradesh1907 Pasteur institute of India, Coonoor , manufactured neural tissue anti-rabies vaccine1920-39 DPT,DT and TT vaccine become available in country1940 Drugs and cosmetics act enacted1948 BCG vaccine laboratory set up Guindy , near Madras (Chennai)1951 Liquid BCG vaccine available in India as part of mass campaigns1965 Live attenuated freeze dried smallpox vaccine become available1967 Freeze dried BCG vaccine become available, OPV become available in India1970 Indigenous OPV trivalent(Sabin) was developed and produced1980 Indigenous measles vaccine production started1984 Inactivated polio vaccine first produced in India (later on production stopped)

16/07/2015


31

Major milestones in vaccine developments and licensing in India

1985/1988 AEFI surveillance system established and initial guidelines were released

1989 Indian vaccine company limited (IVCOL) and Bharat immunological and biological limited (BIBCOL) were set up as public private joint venture companies

1997 First ever recombinant DNA hepatitis B vaccine developed in India

2006 Guideline for clinical trials BY Indian Council of medical research (ICMR)

2009 Three Indian manufacturers developed pandemic flu (Novel H1N1:2009)

2010 National Pharmacovigilance programme of India launched. Meningitis A vaccine for African Meningitis Belt licensed and successfully used in Africa. Indigenously researched bivalent oral cholera vaccine developed and licensed in the country

2012 An indigenous Inactivated JE vaccine licensed in country Indian manufacturer acquired capacity to produce inactivated polio vaccine

16/07/2015


32

List of licensed vaccine manufacturing units in IndiaFollowing manufactures has installed capacity and are licensed for production or marketing of at least one or more vaccine in India

1] BCG vaccine laboratory , Guindy , Madras (Chennai)2] Serum institute of India ,Pune 3] Pasteur institute of India, Coonoor , Tamil Nadu4] Central Research Institute , Kasauli , Himachal Pradesh5] Haffkine Biological product C Ltd. Mumbai6] Human biological and immunological limited, Hyderabad6] Panacea Biotec Ltd. Delhi7] Zydus Cadila , Ahmedabad8] Bharat Biotech International Ltd. Hyderabad9] Bio vaccines, Hyderabad.

16/07/2015


33

List of licensed vaccine manufacturing units in IndiaFollowing manufactures has installed capacity and are licensed for production or marketing of at least one or more vaccine in India

10] King institute of preventive medicine ,Chennai

11] Pasteur Institute , Shillong

12] Dano vaccines, Hyderabad

13] Bharat immunological and biological Company limited, Bulandshahar

14] Bio-med (P) , Ghaziabad

15] Sanofi Pasteur India Pvt. limited , Delhi

16] Sanofi (Aventis)Pasteur , New Delhi

17] Chiron Behring vaccine Lab. Ankles war , Gujarat

18] Bharat biotech International (L) , Hyderabad

16/07/2015


34

Year of start of vaccine manufacturing units in India Year -------------------- Milestone

1832-90 Sporadic research in various setups for development of smallpox vaccine lymph in India

1890 Laboratory in Shillong started producing smallpox vaccine lymph

1897 Plague vaccine produced by Dr.Haffkine in makeshift laboratory of 2 rooms in Grant medical 1898 college , Bombay (Mumbai)

1899 Plague Laboratory ,Bombay: Later on named as Haffkine Institute(1925) Mumbai

1904/05 Central Research Institute , Kasauli , Himachal Pradesh

1907 Pasteur institute of India, Coonoor , Tamil Nadu

1910-30 Additional vaccine institutes established in India , majority of producing smallpox vaccine

16/07/2015


35

Year of start of vaccine manufacturing units in India

Year -------------------- Milestone

1948 BCG vaccine laboratory , Guindy , Madras (Chennai)

1952 Zydus Cadila

1953 Biological E Ltd.

1966 Serum institute of India Ltd.

1982 Indian Immunological Limited

1988 Panacea Biotec

1989 Indian vaccine company limited (IVCOL) and Bharat immunological and biological limited (BIBCOL) 1992 Shantha Biotechnic Ltd.

1996 Bharat Biotech Ltd.

2008 Green Bio-pharma Ltd.

16/07/2015


36

Global monitoring of vaccine :• In the early 1900s,the United States Food And Drug Administration [FDA] and The Paul Ehrlich

Institute in Germany ,were the first regulatory agencies created to ensure the safety of biological products, including vaccines.

• World health organization [ WHO]- - has standard mechanism for assessing the quality of vaccines and that of manufacturing units which provides prequalification of vaccines for procurement for United Nation supply. - This prequalification is considered a standard for vaccine quality. - This prequalification system was developed in 1987 -In order to be included in the list of WHO prequalified vaccines, a vaccine must , inter alia, be licensed and be under continuous regulatory oversight by an independent , fully functioning national regulatory authority in country where the vaccine is manufactured. -Prequalification status normally lasts for two years , after which the vaccine is reassessed to determine if it- and the manufacturer- still meets the standards required to retain prequalification status.

16/07/2015


37

• In this Internationally accepted system of testing vaccines for their efficacy, quality and safety, there are three main testing phases;

1) Preclinical laboratory testing, including animal tests 2) Clinical trials in humans (phase 1-3) 3) post marketing evaluation (phase 4)• A vaccine that has successfully completed the preclinical and clinical trail stages is ready to be

submitted to a regulatory authority for licensure or approval for human use.• A regulatory authority will undertake the review if preclinical and clinical tests, also will inspect

the production site and detailed review the vaccine production from raw to finished product, and will even check the qualification of the manufacturer staff.

• Following licensure, post marketing evaluation involves surveillance for any adverse events. This stage also includes testing pf vaccines batches for consistency of the production process and routine inspection of manufacturing process to ensure continuing conformity to standards of good manufacturing practice(GMP).

16/07/2015


38

• WHO efforts to ensure the safety and quality of vaccines uses a system that- first establishes international standards of vaccine efficacy, safety and quality and then- monitors the extent to which a given licensed vaccine meets the standards.

• Setting of International standards is the role of WHOs Expert Committee on Biological Standardization(ECBS).

• Monitoring of vaccine compliance to these standards is role of the country's National Regulatory Authority(NRA).

• In 1981, WHOs Expert Committee on Biological Standardization(ECBS) called upon all countries to have a national regulatory authority.

• In 1997, WHO started initiative of strengthening of national regulatory authority. In 1997, , only 37(19%) of WHOs 190 member states had a reliable fully functioning national regulatory authority. Out of this, 20(38%) of 52 vaccine producing countries.

• By the end of 2008, only 58(30%) of WHOs 193 member states had a reliable fully functioning national regulatory authority. Out of this, 33(69%) of 48 vaccine producing countries.

16/07/2015


39

Monitoring of vaccine in India :• The regulatory control over quality of drugs in country is exercised through the Drugs &

Cosmetics Act, 1940. The “schedule Y ” of this act regulates clinical and preclinical testing of products.

• As per the Act ,vaccines and other biological products are considered to be “ New drug” and thus are governed by all rules and regulations applicable to a new drug.

• Central Drug Standards Control Organization [CDSCO],which is national regulatory authority (NRA) of India monitors vaccine in India.

• The setting up of vaccine manufacturing units and grant of permission of clinical trails and final licensing and marketing authorization for vaccines is provided by the Central Drug Standards Control Organization [CDSCO].

• As part of licensing process and as post marketing surveillance, the manufacturers are required to submit Periodic safety Update Reports (PSURs) for all newly vaccines to CDSCO, initially every six months in first two years and then annually for next two years.

16/07/2015


40

Monitoring of vaccine in India :• The vaccine manufacturing and procedures for clinical trials have become systematic in India in

recent years.• In 2006, The Indian Council Of Medical Research [ICMR] ,New Delhi , India released a new set of

guidelines for conduct of research on human subjects.• There is section on vaccine research and clinical trials in these guidelines and all vaccine related

trials now need to be registered in clinical trial registry and to be done according to these guidelines.

• The National Pharmacovigilance Programme in India has been launched in July 2010.• India has joined the WHO Global Network of Post Marketing Surveillance(PMS)for new vaccines

with aims to provide useful data for global vaccine safety assurance.• This PMS network of 12 countries from six different regions. In this network ,Maharashtra state

represents India.

16/07/2015


41

Criteria for selection of vaccines for introduction in NIP :• For the selection of vaccine for possible Introduction in NIP ,the below given criteria may be considered

for an informed decision making about the introduction of new vaccine in UIP. 1) Disease burden (incidence/prevalence, absolute number of morbidity/mortality, epidemic/pandemic potential); 2) Safety and efficacy of the vaccine under consideration; 3) Affordability and financial sustainability of the vaccination program, even if the initial introduction is supported by the external funding agency; 4) Program capacity to introduce a new antigen, including cold chain capacity; 5) Availability of a domestic or external vaccine production capacity; 6)The cost effectiveness of the vaccination program and also of the alternatives other than vaccination.

• The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system is one such system followed, which allows a systematic and transparent grading of evidence with deliberate separation of quality of evidence and strength of recommendation.

16/07/2015


42

References:-1. State of the worlds vaccines and immunization, third ed. Geneva, World Health Organization,20092. Vaccines & Biologicals ,Annual Report 2000, Department of Vaccines &Biologicals , Geneva, World

Health Organization,20013. Ivan M. Roitt , Book of Essential immunology ,Blackwell scientific Publications, sixth edition,1988 page

173-1824. William E.Paul (2013), Fundamental Immunology ,Seventh ed.5. Lahariya C. A brief history of vaccines & vaccination in India , Indian J Med Res 139, April 2014, pp 491-5116. Central Drugs Standards Control Organization , Directorate General of Health services , Ministry of health and family welfare , Government of India, New Delhi, 2012 .Available from :http://www.cdsco.nic.in /accessed on 20 June 20157. World Health Organization. A system for the Prequalification of vaccines for UN supply.Geneva,WHO,2012.Available from: http://www.who.int/immunization_standards/vaccine quality/ pq_ system /en /index.html, accessed on 25 June 20158. National vaccine policy ,2011 , Ministry of health and family welfare ,GOI ,New Delhi , April 2011

16/07/2015

http://www.who.int/immunization_standards/vaccine


43

Thank you !!

16/07/2015


44

National Immunization Programme

16/07/2015


4516/07/2015

Introduction to vacciniology

Health & Medicine

Transcript of Introduction to vacciniology