1. Vaccines and infectous diseases

infectious Disease and historically successful eradications

Diseases caused by a pathogen (virus, bacterium, fungus, parasite, or prion) entering a susceptible host . Common pathogens include influenza virus, tuberculosis, HIV and malaria

• Historic successes include smallpox eradication (only human reservoir, global vaccination) and dramatic reductions in polio cases by >99% through immunization . By contrast, lapses in vaccination allow resurgence, as seen in measles outbreaks in communities with low vaccine coverage .

Immune response to infections

1. Innate Immunity (Nonspecific, Immediate)

• First line of defense, present at birth.

• Components:
  

  • Physical barriers: Skin, mucous membranes.

  • Cells: Phagocytes (neutrophils, macrophages), dendritic cells, natural killer (NK) cells.

  • Proteins: Complement system and inflammatory cytokines.

• Mechanism:

  • Recognizes pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (e.g., TLRs).

  • Acts quickly to contain infection through inflammation, phagocytosis, and pathogen destruction.

  • Bridges to adaptive immunity by presenting antigens and releasing signals that activate T and B cells.

2. Adaptive Immunity (Specific & Long-Lasting)

• Takes days to activate, but provides specificity and memory.

Activation and Role of T Cells

• Naïve T cells are activated when antigen-presenting cells (APCs) present pathogen-derived peptides on MHC molecules:
  

  • MHC-I → Activates CD8⁺ cytotoxic T cells → kill infected cells.

  • MHC-II → Activates CD4⁺ helper T cells → coordinate immune responses.

• CD4⁺ T helper cells differentiate into subsets:
  

  • Th1 → Stimulate macrophages (via IFN-γ)

  • Th2 → Help B cells produce antibodies (via IL-4, IL-5)

  • Th17 → Recruit neutrophils (via IL-17)

  • Treg → Suppress immune responses (via IL-10)

Activation and Role of B Cells

• B cells recognize antigens directly via their B-cell receptor (BCR).

• Require T-cell help (from CD4⁺ Th cells) for full activation → occurs in lymph nodes.

• Upon activation:
  

  • Differentiate into plasma cells → produce antibodies (IgM first, then class-switch to IgG, IgA, etc.)

  • Some become memory B cells for rapid future response.

3. Immune Memory

• Memory T and B cells remain after infection or vaccination.

• On re-exposure:

  • Memory B cells → quickly secrete high-affinity antibodies (mostly IgG).

  • Memory T cells → respond faster and more effectively.

• Basis for long-term protection from vaccines.

Active Vs Passive immunity

Activate immunity is when the bodies own immune system is stimulated to produce an immune response (involves memory cells after exposure to an antigen

• take days two weeks to develop

• Long lasting (years or lifelong immune memory)

• Can occur naturally or artificially (vaccines)

• E.g. rabies vaccine

Passive immunity is when pre-formed antibodies are given to an individual providing immediate but temporary

• Immediate protection

• Temporary (weeks to months)

• Naturally (breastmilk ) or artificially

• Eg rabies immunoglobulin given after exposure to provide immediate protection

Complement system ( pathways and outcomes )

• Part of innate immunity; enhances phagocytosis, inflammation, and cell lysis.

• Three activation pathways:

  1. Classical (triggered by antibodies binding to antigen)

  2. Lectin (triggered by microbial sugars)

  3. Alternative (spontaneous activation on pathogen surfaces)

• Main outcomes:
  

  1. Opsonization (C3b): Tags pathogens for phagocytosis.

  2. Chemotaxis (C5a): Attracts immune cells to infection site.

  3. Cell lysis (C5b-C9): Forms the Membrane Attack Complex (MAC) to perforate pathogens.

  4. Inflammation (C3a, C5a): Enhances cytokine release and cell recruitment.

Types of vaccines

• Live attenuated vaccines

• Inactivated vaccines

• Toxoid vaccines

• Viral vector vaccines

Live attenuated vaccines (definition ,mechanisms examples and impact)

• Live-attenuated vaccines: Contain weakened live pathogens (viruses or bacteria) that replicate poorly.

• They mimic natural infection, eliciting strong cellular and humoral immunity with usually one or two doses .

• Advantages: long-lasting immunity, herd effects.

• Limitations: cannot be used in immunocompromised persons; require refrigeration (cold chain).

• Old: MMR (measles, mumps, rubella)

• Newer: Varicella (chickenpox), Rotavirus vaccine

Impact:

·       Measles deaths fell by ~73% globally from 2000 to 2018 due to widespread MMR use.

·       Varicella hospitalizations declined by >85% in countries with high vaccine coverage.

Inactivated vaccines(definition ,mechanisms examples and impact)

• Contain whole pathogens rendered non-replicating by heat/chemicals. They are safer (no risk of infection) but generally less immunogenic, requiring multiple doses or boosters .

• Mechanism: injected antigens are taken up by APCs, eliciting antibody responses. Boosters increase antibody titers.

·       Old: IPV (inactivated polio vaccine)

·       Newer: Inactivated influenza vaccines, Rabies

Impact:

·       Polio: Use of IPV and OPV (oral polio vaccine) has reduced global polio cases by >99% since 1988.

·     Influenza: Reduces hospitalizations and deaths annually, particularly in the elderly.

Toxoid vaccines (definition ,mechanisms examples and impact)

• Use inactivated toxins (toxoids) of bacteria. They induce immunity against the toxin rather than the organism .

• Mechanism: toxoid antigens are processed by immune cells, leading to neutralizing anti-toxin antibodies. Boosters are needed to maintain protection .

·       Old and current: Tetanus and Diphtheria vaccines (DTP)

Impact:

·       Tetanus deaths reduced by ~94% globally from 1988 to 2018 due to maternal and neonatal immunization programs.

·       Diphtheria outbreaks are now rare in vaccinated populations.

 

viral vector vaccines (definition ,mechanisms examples and impact)

• Use harmless “carrier” viruses genetically engineered to express antigens from the target pathogen. The vector (e.g. adenovirus, vesicular stomatitis virus) delivers antigen genes into host cells, producing antigen in vivo.

• These induce strong T-cell and antibody responses, effectively simulating a natural infection without causing disease by the target pathogen.

·       New: AstraZeneca/Oxford and Johnson & Johnson COVID-19 vaccines; rVSV-ZEBOV (Ebola)

Impact:

·       COVID-19: These vaccines played a key role in controlling the pandemic—especially in low-resource settings due to easier storage than mRNA vaccines.

·       Ebola: The rVSV-ZEBOV vaccine helped end major Ebola outbreaks in West Africa and the DRC by rapidly curbing spread.

Clinical trial phases

• Phase I (tens of volunteers) assesses safety and dosage

• Phase II (hundreds) expands safety and checks immunogenicity

• Phase III (thousands+) tests efficacy at preventing disease and further safety .

• Phase IV (post-licensure surveillance) monitors long-term safety and effectiveness.

Ethical issue in vaccine development

• Some trials use human challenge studies (volunteers deliberately exposed to pathogen) to speed efficacy data, but pose ethical questions (especially for novel pathogens) .

• Inclusion of diverse populations (age groups, co-morbidities, pregnant women) ensures vaccines work broadly .

Public health response to unknown vaccine

• Surveillance and outbreak control: Public health agencies (WHO, CDC) conduct disease surveillance to detect cases and monitor trends. Outbreak investigations identify sources, mode of transmission, and implement control (isolation, quarantine, contact tracing, vaccination). Example: ring vaccination (immunizing contacts of cases) was used to eradicate smallpox and contain Ebola outbreaks.

• Herd immunity: When enough people are immune (via vaccination or prior infection), transmission chains break and even unvaccinated individuals are protected. U.S. polio vaccination achieved such a threshold, reducing cases by >99% since 1988 .
  
  Epidemic metrics: Epidemiologists use metrics like incidence (new cases per time), prevalence (total cases at a time), and case fatality rate. They calculate R₀ and effective reproduction number (R). These guide control strategies (e.g. estimating required vaccine coverage).

• 
  Vaccination programs: Routine immunization schedules (EPI) deliver life-saving vaccines to children (e.g. DTP, polio, measles). Mass campaigns and supplemental immunization activities are used in outbreaks (e.g. polio National Immunization Days). The WHO’s Expanded Programme on Immunization (EPI) and Global Vaccine Action Plan coordinate worldwide efforts. Achieving ≥90–95% coverage per vaccine is ideal for herd immunity. Polio and smallpox eradication efforts are classic examples: smallpox was declared eradicated in 1980 through global vaccination; polio is now at the brink of eradication . _

• 
  Global health and One Health: Public health recognizes that human, animal, and environmental health are linked. As research notes, many diseases (zoonoses) require multidisciplinary collaboration (veterinary, medical, ecological). Surveillance in animals (e.g. sentinel chickens for West Nile, poultry H5N1 monitoring) can provide early warning. Integrated approaches (e.g. vaccinating livestock against Rift Valley fever) help prevent human epidemics.

Vaccine hesitancy

• delay in acceptance or refusal of vaccination despite availability . It is context-specific and influenced by “3 Cs”: Confidence (trust in vaccine safety/effectiveness and the health system), Complacency (perceived risk of disease), and Convenience (accessibility) . Hesitancy can apply to specific vaccines (e.g. flu) or populations.

Vaccine misinformation

• 
  
  
  
  Misinformation: False claims about vaccines (e.g. debunked links to autism, microchips, infertility) spread rapidly via social media and can erode confidence. Studies show misinformation drives hesitancy and delays vaccination uptake . For instance, anti-vaccine rumors in Nigeria in the early 2000s led to polio vaccine boycotts and a resurgence of polio cases. In 2015, a measles outbreak at a California theme park was traced to under-immunized communities influenced by vaccine fears .

Consequences of vaccine hesitancy and how to address it.

• Consequences: Hesitancy undermines herd immunity, enabling outbreaks of preventable diseases. Recent years have seen measles resurgences in the U.S., Europe, and elsewhere Misinformation can also affect newly introduced vaccines (e.g. COVID-19).

• Addressing hesitancy: Public health strategies include transparent communication, engagement with communities, addressing concerns, and fighting misinformation (fact-checking, partnerships with media). Examples of success: High-profile endorsements and school requirements have increased uptake of HPV and MMR vaccines. WHO declared vaccine hesitancy a top global health threat in 2019. Surveys and interventions (e.g. tailored messaging by trusted providers) are used to rebuild confidence.

What are emerging diseases ( EIDs) and why are they relevant

Emerging infectious diseases (EIDs): Diseases caused by new pathogens or known pathogens in new contexts.

EID outbreaks often start from an animal spillover (zoonotic origin) and can cause epidemics or pandemics . ie COVID-19, SARS (2003), and novel influenzas (H5N1, H1N1)

Environmental changes (urbanization, deforestation), climate change, and global travel heighten spillover and spread .

The 1918 influenza pandemic (kills ~50M) was an early 20th-century example of catastrophic emergence .

Relevant cause they can cause a lot of deaths.

Re-emerging diseases

Diseases once under control that reappear. Examples: TB (especially drug-resistant TB), measles (where vaccination dips), cholera outbreaks, and even polio reappearances in areas after interruptions.

Antimicrobial resistance (e.g. MRSA, drug-resistant malaria) creates treatment-refractory “reemergence.”

Global warming expands vector ranges, leading to dengue, chikungunya, Lyme disease in new areas.

Drivers of disease emergence

Drivers of emergence: Research explains, climate change can expand reservoirs and vectors (e.g. warmer temperatures allow mosquitoes to survive longer), increasing EID risk.

Rapid population growth and travel mean a local outbreak can spread worldwide before detection. For example, Zika virus emerged unexpectedly in the Americas (2015–16), causing congenital defects

What has the COVID pandemic taught humans about disease surveillance ?

• The SARS-CoV-2 pandemic underscores the need for global surveillance networks and rapid response. Initiatives like WHO’s Global Outbreak Alert and Response Network (GOARN) and genomic surveillance (e.g. GISAID for influenza and SARS-CoV-2) aim to detect EIDs early.

• One lesson: a worldwide framework using new tech (AI modeling, real-time data) is needed to forecast disease under changing climate and mobility .

• Case example – COVID-19: Emerged late 2019 from likely animal source. Its rapid mutation gave rise to variants (Delta, Omicron) that challenged vaccines and control measures. The pandemic highlighted how even novel pathogens can become endemic if not contained, emphasizing continual vigilance for re-emergence (e.g. new SARS, MERS strains).

CS&E - COVID-19 pandemic (2019–2025):

• A novel coronavirus caused a global pandemic. Within one year, multiple vaccines were authorized (mRNA, vector, protein platforms) and ~67% of world population received at least one dose by November 2023 (though unevenly) .

• estimated COVID-19 vaccines prevented estimated 14 million deaths in 2021 alone .

• Challenges included viral variants (requiring booster campaigns) and vaccine inequity: approximately >70% in high-income countries vs approximately ~30% in low-income (2021) .

CS&D- Malaria

• Malaria: A mosquito-borne parasitic disease causing ~627,000 deaths/year (mostly children in Africa).

• For decades no vaccine was available, but RTS,S/AS01 (protein-based) was WHO-recommended in 2021, and a second vaccine R21/Matrix-M got WHO recommendation in Oct 2023 . Both are safe and partially effective in young children (efficacy ~30–75% in trials). As WHO notes, high vaccine demand far exceeds supply, but adding R21 aims to cover more children in endemic areas . These are historic firsts for malaria, expected to save hundreds of thousands of lives .

CS&D- Human papilloma virus

• A sexually transmitted virus causing cervical cancer. Vaccines (Gardasil, Cervarix) use VLP subunits of HPV capsid proteins.

• High coverage in adolescent girls has sharply reduced HPV infections and precancerous lesions; Australia is on track to eliminate cervical cancer. This is a success of vaccinating before exposure.

How is Australia on track to eliminate cervical cancers?

• Due to comprehensive approach which combines HPv vaccination, cervical screening and effective strategies.

• Since 2007 Australia has progressively adopted a publically funded HPV vaccination program targeting 12 to 26 year old boys and girls this saw a decline of HPV type 16 and 18 among women between the age of 18-24 dropped from 22.7% before vaccination to 1.5% in 2015 -2017.

CS&D- Polio

• Contagious viral disease which attacks The nervous system. It can cause flu symptoms, brain inflammation, and paralysis.

• It is passed through person to person contact

• Once endemic worldwide, polio cases have fallen >99% since 1988 due to global vaccination (oral and inactivated polio vaccines). Only two countries remain endemic (2025).

• Polio vaccine requires multiple doses for immunity, and programs have built robust surveillance systems. Polio exemplifies how sustained immunization can near-eradicate a disease .

CS&D- measles

• Highly contagious; outbreaks continue when coverage dips.

• Recent case: 2019 Samoa epidemic (over 80 deaths) was linked to a drop in MMR uptake amid vaccine scare.

• In the U.S., measles resurged in 2019 after measles was declared eliminated. These show how hesitancy (and access issues) can undo public health gains.

CS&D- Ebola

• Ebola (2014–2016 West Africa): A deadly filovirus outbreak sparked accelerated vaccine R&D. The rVSV-ZEBOV Ebola vaccine (a live recombinant vesicular stomatitis virus vector) was developed and deployed in 2019.

• Trial data showed high efficacy. Subsequent outbreaks in DRC used ring vaccination with this vaccine.

• Ebola highlights the role of targeted outbreak vaccination and international cooperation.

What is ring vaccination?

Giving vaccine to people who come in contact with infected individuals thus reducing people with the disease (because you’re targeting people who have come into contact with others who have the disease).

Challenges in vaccine implementation

• Equity & access

• Logistics and cold chain

• Public acceptance

• Manufacturing and supply

• Viral evolution

• Implementation in complex settings (conflict zones, remote regions)

Challenges- Equity and access

Global disparities persist. As modeled for COVID-19, vaccine rollout averted most deaths in high-income countries; low-income countries had far lower vaccination rates, limiting impact .

For example, in 2021 only approximately 10.9% of people in low-income countries had received a COVID-19 vaccine dose. COVAX and other initiatives aim to improve equity, but issues like nationalism and supply bottlenecks remain.

Even before COVID-19, routine coverage lagged: in 2018 about 20 million infants missed life saving vaccines like DTP and measles, nearly half of which are children living in low income countries indicating gaps in immunization programs.

Challenges- logistics and cold chain

Many vaccines require temperature control. Some (mRNA COVID-19 vaccines) need ultra-cold storage (–70 °C), while others need 2–8 °C. UNICEF and partners invested heavily in cold chain capacity globally .

Delivery to remote areas can involve planes, boats, and on-foot transport, with refrigerators or cold boxes to keep doses viable . Interruptions (power outages, long transport) risk spoilage.

For new vaccines, improving thermostability is a priority (e.g. lyophilized formulations).

Challenges- public acceptance

Hesitancy and misinformation remain obstacles to high uptake. Even with available supply, people may refuse or delay vaccination.

Tailored communication campaigns and community engagement are needed to overcome fears and cultural barriers.

Challenges- manufacturing and supply

Producing billions of doses requires large-scale facilities and raw materials (e.g. bioreactors, lipids for mRNA). During the COVID-19 pandemic, rapid scale-up led to occasional shortages of syringes and vials.

Building flexible manufacturing networks is critical. Intellectual property and patent issues can also affect global vaccine licensing and technology transfer.

Challenges- viral evolution

Pathogen mutation can reduce vaccine effectiveness. Seasonal influenza strains evolve (antigenic drift), requiring annual vaccine updates.

SARS-CoV-2 variants (Delta, Omicron) decreased COVID vaccine protection against infection, necessitating booster shots and new formulations.

Ongoing surveillance of viral genetics and adaptable vaccine platforms (e.g. mRNA with quick re-formulation) are essential to meet this challenge.

Challenges- implementation in complex settings

Conflict zones, remote regions, and marginalized communities pose logistical and trust barriers. Political instability can disrupt immunization campaigns.

Vaccine storage and administration infrastructure may be lacking in low-resource settings, requiring international support.

Moreover, ensuring timely follow-up doses (multi-dose schedules) can be difficult where healthcare access is limited.