Topic: Covid-19 Vaccines - Forging a Path to a Post Pandemic World

3^rd July, 2021, Saturday, 9.30am-10.30am

Key points from the discussion

A presentation on “Covid-19 Vaccines - Forging a Path to a Post Pandemic World” was given by Dr Monica Vasudev, Allergist Immunologist, Advocate Aurora Health, Wisconsin, USA.

• The immune system is the natural ability of the body to defend against pathogens. There are two types of immunity: Innate immunity, which is the first line of defence and is the general immediate response to any infection; adaptive immunity, which is the second line of defence and is the specific response to the infection.
• The innate immune response occurs immediately, while the cellular and antibody response usually starts after 6-8 days.
• Adaptive immunity - humoral and cell-mediated immunity - is activated by infection and immunisation.
• In SARS-CoV-2 infection, both virus specific B-cell mediated humoral immunity and T-cell mediated cellular immunity have been implicated in recovered Covid-19 patients.
• Neutralizing antibodies change the viral spike protein and prevent virus entry into the cell. Antibodies that attach differently may not effectively neutralize the virus. Antibodies to other components of the virus may not effectively neutralize the virus. Antibodies target different parts of the spike protein, which is a trimeric protein.
• Antibodies can appear 1-3 weeks after symptoms appear. The immune response varies between asymptomatic and symptomatic infections. The levels of neutralizing antibodies appear to be higher in persons with more severe disease.
• The usefulness of monitoring antibody response as a measure of presence and duration of immunity to SARS-CoV-2 is unknown. Antibodies may last not more than 10 months. However, T cells have the ability to recall and initiate immune responses.
• Those with low level neutralizing antibodies, the innate and T cell response may clear the virus. Even without detectable antibodies, persons exposed to the virus may develop specific T cell responses.
• The potential applications of an effective Covid-19 vaccine include prevention of infection/transmission/disease/hospitalization/ICU admission/death.
• History shows that development of a vaccine has always taken years. Research for an HIV vaccine is still ongoing. Covid-19 vaccines have been developed just within a year.
• The vaccine design and clinical trials started almost immediately after the Covid-19 pandemic came to light in December 2019. The SARS-CoV-2 was sequenced on January 10, 2020. The key target was the spike protein of the virus.
• Several vaccine platforms have been utilised; RNA vaccines (Pfizer, Moderna), DNA vaccines, inactivated vaccines (Sinovac, Sinopharm, Covaxin), viral vector vaccines (AstraZeneca, J&J), subunit vaccines (Novavax) and live attenuated vaccines
• The SARS-CoV-2 can carry both forms of the spike protein, the prefusion and postfusion spike protein, on its surface without needing to bind to the ACE2 receptor.
• The estimated vaccine effectiveness of Pfizer-BioNTech vaccine a week after the second dose was 92% for documented infection, 94% for symptomatic infection, 87% for hospitalization and 92% for severe Covid-19 (NEM, 2021).
• As per RDIF, Sputnik V demonstrates 97.6% efficacy according to analysis of data from 3.8 million vaccinated persons in Russia. This makes it the most efficient vaccine in the world. Sputnik V vaccine is approved for use in 60 countries. It is the second vaccine to get the most number of approvals by government regulators.
• The Pfizer and Oxford-AstraZeneca vaccines were both 80% effective at preventing Covid-19 hospitalizations in older adults in a study from the UK.
• The Pfizer and Moderna vaccines have shown 100% and 93% protection in adolescents aged 12-15 years.
• Antibody-dependent enhancement occurs when vaccines produce antibodies, which interact with the virus to enhance the damage. ADE is most classically associated with dengue. There is no evidence yet of ADE from vaccine trials.
• Pfizer and AstraZeneca Covid-19 vaccines (both doses) have shown efficacy against the delta B.1.617.2 variant in a Public Health England study; ~88% and ~60% respectively. However, effectiveness reduced to 33% after single dose of both vaccines.
• The B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from Covid-19 convalescent and Moderna and Pfizer vaccinated individuals.
• The delta variant is B an immune evasion variant with increased capacity to enter and fuse lung cells.
• Pfizer and Moderna vaccines produce long lasting immunity. These m-RNA vaccines induce a persistent germinal cell B cell response, enabling generation of robust humoral immunity.
• Hybrid immunity is when natural immunity is combined with vaccine-induced immunity resulting in 25-100 times higher antibody responses, driven by memory B cells and CD4 T cells. It provides broader crossprotection from variants.
• Mixing vaccines leads to higher reactogenicity and more common vaccine-related side effects such as fever.
• Data from UK Com-COV study show increased antibodies to spike proteins when AstraZeneca vaccine was given followed by Pfizer four weeks later.
• Similarly, the Spanish CombivacS trial of AstraZeneca followed by Pfizer showed that the antibody response to Pfizer was even stronger than that observed after taking both doses of AstraZeneca vaccine.
• The Novavax vaccine overall has 90% effectiveness (PREVENT-19). It offers 91% protection to people at high risk of a poor outcome and is 93% protective against predominantly circulating variants of concern.
• Testing for neutralizing antibodies to RBD is very difficult. If it is present, it can help with immunity in vaccinated persons. cPass Technology is used to look for neutralizing antibodies to RBD.
• Availability of the vaccine is more important than the choice of the vaccine.
• Choose a vaccine which utilizes a different mechanism of action for the booster dose.
• Covid-19 may become endemic and require frequent immunisations.
• Concomitant administration of Covid and flu vaccine is safe.
• Myocarditis after Pfizer vaccine has been reported mostly in boys (16-21 years), it is mild and was treated with NSAIDs.
• R0 (nought) is different for different variants. Hence, herd immunity is a moving target.
• Vaccine responsiveness is difficult to assess with the tools that we have.
• If there are lot of breakthrough infections and hospitalizations, this means that the vaccine is probably not effective. If vaccine antibodies are not detectable, this does not mean high risk unless the rate of infection is very high.

Participants

Member National Medical Associations

Dr Yeh Woei Chong, Singapore, Chair CMAAO

Dr Ravi Naidu, Malaysia, Immediate Past President CMAAO

Prof Ashraf Nizami, Pakistan, First Vice President CMAAO

Dr Alvin Yee-Shing Chan, Hong Kong Medical Association, Treasurer, CMAAO

Dr Marthanda Pillai, India Member World Medical Council

Dr Angelique Coetzee, South Africa

Dr Akhtar Hussain, South Africa

Dr Debora Cavalcanti, Brazil

Dr Salma Kundi, Pakistan

Dr Qaiser Sajjad, Pakistan

Dr Md Jamaluddin Chowdhury, Bangladesh

Dr Mukti Shrestha, Nepal

Dr Marie Uzawa Urabe, Japan

 Invitees

 Dr Monica Vasudev, USA

Dr Nidhi Aggarwal, USA

Dr Shashank Joshi, Mumbai, India

Dr Mulazim Hussain Bukhari, Pakistan

Dr Chew Lip

Dr Derek Tse

Dr Kim Shang Lee

Dr Lim Li Ling

Dr Cheng Soo Hong

Dr Lim Bee Lin

Dr Tammy Chan

Dr Teow Kay Leong Roy

Dr Yang Ing Woei

Dr Kwong Kum Hoong

Dr Lee Kim Shang

Dr YV Lee

Dr Geok Jim

Dr Goh MH

Dr HM Chang

Dr Ian OW

Dr Michael Wong

Dr Ng CW Mark

Dr Yeo Tseng Tsai

Dr Vincent Chow

Dr Teo Tiong Kiat

Dr Ai Mian Chia

Dr Cheng Soo Hong

Dr Ching Ching

Dr S Sharma, Editor IJCP Group

Moderator

Mr Saurabh Aggarwal