Immunity and vaccination to Influenza H 1 N

Immunity and vaccination to Influenza H 1 N 1 – swine flu Mohammad S. Khalifeh Assistant Professor, Immunobiology Department of Veterinary Basic Medical Science Department of Molecular Biology and Genetic Engineering Jordan University of Science and Technology Technical consultant Jordan biological Diagnostics Jordan Bio-industrial Center (JOVAC)

KNOWLEDGE IS OUR BEST DEFENSE

The principle immunity to infection

The principle immunity to infection

Mechanisms of adaptive and innate immunity

Influenza Genes • Influenza A viruses have 8 gene segments that encode 10 polypeptides • • Segment 1 (2, 341 nt): PB 2 (RNA transcriptase) Segment 2 (2, 341 nt): PB 1 (RNA transcriptase) Segment 3 (2, 233 nt): PA (RNA transcriptase) Segment 4 (1, 778 nt): HA (hemagglutinin) - 16 known subtypes Segment 5 (1, 565 nt): NP (nucleoprotein) Segment 6 (1, 413 nt): NA (neuraminidase) - 9 known subtypes Segment 7 (1, 027 nt): M 1, M 2 (matrix proteins) Segment 8 (890 nt): NS 1, NS 2 (inhibits m. RNA splicing and IFN response; nuclear export signal for viral RNPs)

Immunity to Influenza Virus Neutralization YY Y Y HA Y Heterotypic Abs react with proteins of influenza Virus rather than HA and NA Antibody-mediated Opsonization

!!!? What’s the Problem Immunopathogenesis and genetics

Type “A” Influenza Viruses Identified by 2 Surface Protein Structures Combinations “H” - Hemagglutinin (1 – 16) Entry into Cell “N” - Neuraminidase ( 1 - 9) Exit from Cell 144 Possible combinations

Antigenic Drift H 1 N 1 • Imperfect “manufacturing” of virus – Small changes in H and N – Partial immunity in population • Incomplete protection; still get sick • Need new flu vaccine every year ur c c o cs i em Ye a rly id p e H 1 N 1 This One I Know…. . But H 1 N 1 “Do I know you? You look vaguely familiar!”

Antigenic Shift H 1 N 1 H 1 N 1 c i em he t s D e riv cu c o c n e rr fa o e nd a p H 1 N 1 Black is my favorite I am Color blind Oh my god…I don’t know you at all !!! This is all what I am seeing

Feedback inhibition Vs Heterotypic Abs

Will a current flu vaccine protect me from Swine Flu? Answer: No Vaccines containing the 2008– 09 trivalent vaccine virus strains include: • A/Brisbane/59/2007 (H 1 N 1), • A/Brisbane/10/2007 (H 3 N 2), and • B/Florida/4/2006 • All 3 vaccine virus strains were changed for the 2008 -2009 season 2007 -2008 Vaccine Strains: A/Solomon Islands/3/2006 (H 1 N 1), A/Wisconsin/67/2005 (H 3 N 2), and B/Malaysia/2506/2004 viruses

Influenza Vaccines • Inactivated (TIV) – intramuscular – trivalent – contains egg protein • Live attenuated vaccine (LAIV) – intranasal – trivalent – contains egg protein

Inactivated Influenza Vaccine Efficacy • Duration of immunity for inactivated influenza vaccine is considered to be 1 year or less • The vaccine is actually effective two weeks after the shot is given. • 70%-90% • 30%-40% • 50%-60% • 80% effective among healthy persons <65 years of age effective among frail elderly persons effective in preventing hospitalization effective in preventing death

A pandemic soon…. . Will A Vaccine Be Easy to Produce? • There will be little or no vaccine until 6 - 9 months after the outbreak begins • Production process is slow – 3 -6 months until first doses are available – Longer until enough to cover all high-risk groups and general population – For seasonal influenza, viruses are grown in chicken eggs for 7 days to produce high-enough titers for vaccines – Avian influenza viruses kills eggs in 4. 5 days – An insufficient titer is generated for vaccines • The world’s annual vaccine capacity is 300 million doses

Challenges • Vaccine Supply (annual uncertainty) • Recommendation vs. prioritization of high-risk groups • Vaccine Distribution (pre-booking) • Vaccine delivery • Vaccine Funding and over-reliance on public health

Live Attenuated Influenza (Vaccine (LAIV • Approved only for healthy persons 2 years through 49 years of age who are not pregnant – healthcare personnel – persons in close contact with high-risk groups – persons who want to reduce their risk of influenza MMWR 2008; 57 (RR-7)

Influenza Vaccination • Influenza activity can occur as early as October • Continue to vaccinate throughout influenza season (December-March) • Pregnancy and Influenza Vaccine MMWR 2008; 57 (RR-7)

“It would be better to have an immunization program without an epidemic than an epidemic without an immunization program. ” (CDC, 1976)

USA guidelines for vaccine priority groups? Tier 1 A B C D Tier 2 A B Vaccine Producers direct care medical workers Persons > 65 with compromising conditions Pregnant women; Household contacts of compromised persons Public health emergency responders and key public officials. Healthy 65 and older and children Emergency response, essential services Tier 3 Key government and society leaders Tier 4 Healthy Persons

The only thing more difficult than planning would be explaining why you did not do it! -- Marja Esveld Healthcare Inspectorate, The Netherlands

Cold vs. “Flu” (influenza) Symptoms Cold Flu Fever rare characteristic Headache mild (sinus) strong Aches & Pains slight usual, strong Fatigue mild 2 -3 weeks Exhaustion never early, profound Stuffy nose usual sometimes Sneezing usual sometimes Sore throat common sometimes Chest discomfort mild common, strong

WHO Phases of a Pandemic Interpandemic Phase I No new virus in humans Phase 2 Pandemic Alert Phase 3 Phase 4 Pandemic Phase 5 No new virus in humans New virus in humans Small clusters, localized Larger clusters, localized Animal virus, low virus, high risk to humans Little/no spread among humans Limited spread among humans Current level Phase 6 Increased and sustained spread in general population

Lab Testing • Preferred specimen: nasopharyngeal/nasal swab, wash, aspirate • Rapid influenza tests – Results within 30 minutes – May determine type (A vs. B) – High false negative results (30%) • Viral culture – Results in 3 -10 days – Determine specific subtype or strain – reference standard of diagnosis • Not necessary to test all patients – – – May not affect clinical decision-making Expensive Labor intensive Cohort hospitalized patients Outbreaks