CME INDIA Presentation by Dr. Mahadev Desai, Sr. Consultant Physician, D. City Centre, Ahmedabad.
Based on a presentation at APICON-2023 at Ahmedabad.
Quick Take-Aways
We fight any infection with Innate and Adaptive Immunity. |
Innate immunity is non-specific and our first defence to stop or restrict any infection. |
Adaptive immunity is disease-specific, acquired slowly, may wane with time. |
Herd immunity is protection of unvaccinated person by naturally infected person or vaccinated persons. |
Hybrid immunity is the combination of immunity acquired by natural infection and vaccination and gives better protection. |
Since natural infection carries many risks of complications of disease like hospitalization, death, long term sequalae, Mass Vaccination is our best shot to tackle any epidemic. |

How does Herd Immunity work?
- When a high percentage of the population is vaccinated or naturally infected, it is difficult for infectious diseases to spread from person to person, because there are not many people who can be infected.
- Herd Immunity is also called Herd Protection or Community Immunity or Mass Immunity.

Who depends on the Herd Immunity the most?
Some people in the community rely on herd immunity to protect them. These groups are particularly vulnerable to disease, but often cannot safely receive vaccines:
- Many hospitalized ill patients.
- Elderly people.
- Newborn babies.
- Pregnant women.
- Immunocompromised situations e.g.,
- People with HIV.
- Diabetes.
- Receiving steroids or Chemotherapy.
- Those without a working spleen.
Limitations of Herd Immunity
- Herd immunity does not give a high level of individual protection.
- Herd Immunity wanes with time.
- Herd immunity does not protect against all vaccine-preventable diseases e.g., Tetanus.
Does Herd Immunity differ from Disease to Disease?
- Yes
- Development of Herd Immunity depend upon many factors:
- R0 number (R nought) – Basic reproduction number of the disease: the average number of people an infected person goes on to infect in a completely susceptible population.
- R0 number estimated to lie for:
- COVID-19*: between 2.5 and 3
- Seasonal Flu: between 0.9 and 2.1
- Measles: between 12 and 18
What is Hybrid Immunity?
- Immunity which is provided by combination of natural infection and vaccination.
- Convalescent people receiving vaccine were found to have neutralizing antibody titers on average 50-fold higher than unvaccinated convalescent individuals.
- Provides better protection against subsequent COVID-19 infection than either vaccination or infection alone:
- higher antibody levels
- less frequent infection.
- less severe infection.
Immune Protection with Infection, Vaccine and Both

Credit: Suryawanshi, R., Ott, M. SARS-CoV-2 hybrid immunity: silver bullet or silver lining?
Nat Rev Immunol 22, 591–592 (2022). https://doi.org/10.1038/s41577-022-00771-8
Understanding the above figure
- a – Emerging Omicron sub-variants escape immunity conferred by infection with non-Omicron SARS-CoV-2 variants.
- b – A second dose of mRNA vaccine gives moderate protection for non-Omicron and limited protection against Omicron variants 6–8 months post-vaccination.
- c – Hybrid immunity elicited by BA.1 breakthrough infection in vaccinated individuals (2 doses) provides cross-variant protection but causes neutralization escape for newly emerging Omicron variants.
- d – Hybrid immunity generated by Delta infection in vaccinated individuals elicits broader protection against non-micron and Omicron (BA.1) variants.
- e – Compared with B.1.617.2, immune imprinting generated by infection with Wuhan/ B.1.1.7, vaccination (3 doses) and Omicron reinfection decreases Omicron neutralizing antibodies and T cell recognition, which may increase chances of Omicron reinfection.
Hybrid Immunity against BA.2 reinfection
- New study shows that health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant.
Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression (Ref-2)

Should we try to achieve Hybrid Immunity for All?
- Hybrid immunity cannot be the goal for public health as it comes with a price, and we cannot encourage people to catch infection by lowering the guards.
- Consequences of acute as well as long-term complications are too well known to all of us.
- Covid-appropriate behaviour needs to be implemented whenever a new immuno-evasive variant (BQ.1.1 or XBB) has surfaced in a locality.
- Urgent need remains the mass vaccination covering as many persons as possible.
Covid-19 Statistics in India

- Total No. of Covid-19 cases: 4.41 Crores
- Total No. of Deaths: 5.31 Lacs
Path Ahead
- While hybrid immunity may not be the silver bullet to end the SARS-CoV-2 pandemic, it is a silver lining, from which we can learn to move to the next level of vaccine design and delivery.
References:
1. Suryawanshi, R., Ott, M. SARS-CoV-2 hybrid immunity: silver bullet or silver lining? Nat Rev Immunol 22, 591–592 (2022). https://doi.org/10.1038/s41577-022-00771-8
2. Niklas Bobrovitz et alLancet Infect Dis 2023 Published Online January 18, 2023 https://doi.org/10.1016/ S1473-3099(22)00801-5
3. Sara Carazo et alLancet Infect Dis 2023; 23: 45–55 Published Online September 21, 2022 https://doi.org/10.1016/ S1473-3099(22)00578-3

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In india Hybrid Immunity has been robust as to ward off more than 300 variants of Omicron. Review article is based on mRNA Vaccine which induce immunity against very specific epitopes of Spike protein. Vaccines Used in India coupled with natural infection created the best response
Entirely agree with you Sir.