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Vaccines vs. COVID-19: A Race for Safety

How vaccines combat COVID-19 and adapt to new variants.

Sandhya Bangaru, Abigail M. Jackson, Jeffrey Copps, Monica L. Fernández-Quintero, Jonathan L. Torres, Sara T. Richey, Bartek Nogal, Leigh M. Sewall, Alba Torrents de la Peña, Asma Rehman, Mimi Guebre-Xabier, Bethany Girard, Rituparna Das, Kizzmekia S. Corbett-Helaire, Robert A. Seder, Barney S. Graham, Darin K. Edwards, Nita Patel, Gale Smith, Andrew B. Ward

― 6 min read


COVID-19 Vaccine Insights COVID-19 Vaccine Insights against COVID-19 variants. Examining vaccines and immune responses
Table of Contents

The COVID-19 pandemic brought about a swift and urgent need for vaccines to combat the spread of the virus known as SARS-CoV-2. In record time, effective vaccines were created and distributed globally. This effort was comparable to a race against time, as researchers worked tirelessly to keep the virus at bay.

How Vaccines Work

Vaccines train our immune systems to recognize and fight off infections. When vaccinated, the body learns to recognize parts of the virus, making it easier to deal with real infections later on. Most COVID-19 vaccines focus on the Spike Protein of the virus, which plays a key role in helping the virus enter human cells.

When the body detects the spike protein, it produces Antibodies. These antibodies are like little warriors ready to battle the virus if it tries to invade again. The vaccines can create these antibodies in both people who have never had the virus and those who have already been infected.

Types of COVID-19 Vaccines

Several types of COVID-19 vaccines have been created, each using different methods to stimulate the immune system. Here are a few notable examples:

MRNA Vaccines

The mRNA vaccines, like those developed by Moderna and Pfizer-BioNTech, use a piece of genetic material called messenger RNA (mRNA) that instructs cells to make a harmless piece of the spike protein. This trains the immune system without using the live virus.

Viral Vector Vaccines

Another type is the viral vector vaccine, such as the one from Janssen. This method uses a different virus (not the one that causes COVID-19) as a delivery system to introduce instructions for building the spike protein.

Protein Subunit Vaccines

There are also protein subunit vaccines like Novavax, which contain harmless pieces of the virus (proteins) instead of the whole virus or its genetic material.

All these vaccines aim to get the body ready to fight off the actual virus if it ever comes knocking.

The Challenge of Variants

While the initial vaccines were successful in reducing infections, the emergence of new variants of the virus has posed challenges. Some variants can partially escape the immune response triggered by the vaccines. The Omicron variant, for example, has shown the ability to evade immune defenses in some cases, making it necessary for scientists to adapt and improve vaccines continually.

Booster Shots

Booster shots have been introduced to help strengthen the immune response and improve protection against these variants. Both monovalent (targeting one spike protein) and bivalent (targeting multiple variants) boosters have shown to enhance antibody responses. However, maintaining long-lasting immunity remains a work in progress.

Understanding Spike Protein and Antibodies

The spike protein is vital in the effort to design vaccines. By targeting this protein, vaccines can generate antibodies that neutralize the virus. Neutralizing antibodies, often referred to as nAbs, bind directly to the spike protein and prevent the virus from entering cells.

Different Parts of the Spike Protein

The spike protein has several regions of interest:

  • Receptor-Binding Domain (RBD): This is where the spike protein attaches to human cells, and most neutralizing antibodies target this area.
  • N-Terminal Domain (NTD): Another region that can trigger an immune response, though it's less clear how antibodies against this area work.
  • S2 Region: This part is involved in the actual fusion of the virus with the host cell.

Research has indicated a variety of antibodies can target both the RBD and NTD, playing different roles in the protective immune response.

Characterizing Antibody Responses

Scientists study antibodies to understand how well vaccines work and how they might be improved. By isolating and analyzing these antibodies from vaccinated individuals, researchers can build a clearer picture of the immune response.

Monoclonal vs. Polyclonal Antibodies

Antibodies can be monoclonal (from a single type of immune cell) or polyclonal (from multiple cell types). Monoclonal antibodies are often used in treatments and can be characterized precisely, while polyclonal antibodies are the body's natural response to infections or vaccinations.

Polyclonal antibodies offer a broader defense against the virus, as they can target multiple regions of the spike protein. Their diversity plays a vital role in protecting against different strains.

The Role of Electron Microscopy

Advanced techniques like electron microscopy help researchers visualize the antibodies bound to the virus. This technology allows scientists to see how effectively the antibodies target the spike protein and can lead to insights for better vaccine designs.

Observing Responses in Different Groups

Studies have looked at how different vaccines perform in clinical trials and in various populations. For example, researchers tested the responses to both mRNA and protein subunit vaccines in non-human primates (NHPs) and human trial participants.

Responses from Non-Human Primates

In studies with NHPs, researchers observed similar patterns of antibody responses between the two types of vaccines. Both types elicited strong responses, particularly against the spike protein.

NHPs help scientists understand how long-lasting and effective the immune response may be, as they are more similar to humans than other models for testing.

Responses from Clinical Trial Participants

Clinical trial participants also showed promising responses. Vaccine recipients developed a variety of antibodies targeting different regions of the spike protein. Analysis revealed that some participants had higher levels of certain types of antibodies, suggesting differences in how well different vaccines worked.

The Importance of Antibody Diversity

Diversity in the antibody response is important because it increases the chance of neutralizing the virus effectively, particularly against emerging variants. The more types of antibodies the body can produce, the better the defense against a changing virus landscape.

Analyzing Antibody Specificities

Researchers analyze the specific types of antibodies generated by different vaccines. They look for patterns that indicate how well a vaccine can protect against variants. For example, NTD-targeting antibodies have been shown to struggle against variants, which is an important consideration for future vaccine development.

Limitations and Ongoing Research

While vaccines have been a critical tool in fighting COVID-19, they are not a one-size-fits-all solution. The emergence of variants means that vaccines need to be adjusted and improved continuously. Research continues to seek new targets and strategies to enhance vaccine effectiveness.

Future Directions

Scientists are also looking at how to create vaccines that can induce a stronger response to highly variable regions of the virus. Understanding which types of antibodies work best can help in the design of future vaccines.

Additionally, there is ongoing work to monitor antibody responses over time to assess how long immunity lasts and how it changes with different variants.

Conclusions

The race against COVID-19 has shown tremendous progress in vaccine development and our understanding of antibody responses. As researchers continue to learn more about how to adapt vaccines to tackle new variants, the goal remains clear: protect people from COVID-19 effectively while keeping pace with a rapidly changing virus.

In the end, it’s a bit like playing whack-a-mole with a very slippery and crafty opponent, but with science as our trusty mallet, we are making strides toward winning this game.

Original Source

Title: Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines

Abstract: Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors. Both vaccines induce diverse polyclonal antibody (pAb) responses to the N-terminal domain (NTD) in addition to the receptor-binding domain (RBD) of the Spike protein, with the NTD supersite being an immunodominant epitope. High-resolution cryo-EMPEM studies revealed extensive pAb responses to and around the supersite with unique angles of approach and engagement. NTD supersite pAbs were also the most susceptible to variant mutations compared to other specificities, indicating that ongoing Spike ectodomain-based vaccine design strategies should consider immuno-masking this site to prevent induction of these strain-specific responses.

Authors: Sandhya Bangaru, Abigail M. Jackson, Jeffrey Copps, Monica L. Fernández-Quintero, Jonathan L. Torres, Sara T. Richey, Bartek Nogal, Leigh M. Sewall, Alba Torrents de la Peña, Asma Rehman, Mimi Guebre-Xabier, Bethany Girard, Rituparna Das, Kizzmekia S. Corbett-Helaire, Robert A. Seder, Barney S. Graham, Darin K. Edwards, Nita Patel, Gale Smith, Andrew B. Ward

Last Update: 2024-12-12 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.11.628030

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.11.628030.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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