Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution

Round 1

Reviewer 1 Report

This paper reports on Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution. This is a very interesting review presenting a novel topic with large potential which is generally well-written. The text is consistent and clear. Therefore, I recommend publishing the manuscript in Vaccines after minor corrections which of them are listed below:

1.     Authors in the new para can discuss immune response to booster dose and how it could be useful in vaccine development (for each Strategy).

2.     You can summarize each Strategy in a table with more details.

Author Response

This paper reports on Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution. This is a very interesting review presenting a novel topic with large potential which is generally well-written. The text is consistent and clear. Therefore, I recommend publishing the manuscript in Vaccines after minor corrections which of them are listed below:

1. Authors in the new para can discuss immune response to booster dose and how it could be useful in vaccine development (for each Strategy).

A new paragraph is added to 292-301

A summary paragraph has been added for each strategy

2. You can summarize each Strategy in a table with more details.

The table is added, as shown in Table 1 in the article

Table 1. COVID-19 vaccine responds to the evolution of the virus in development

Reviewer 2 Report

The authors compile a more recent review of current and potential vaccines for COVID-19 and sarbecoviruses.  This review would be significantly improved by stating that the review will concentrate on the appearance of the VoC Omicron strain to alert the reader that this is the focus of the review. If not a significant amount of work is required to edit this review. I have some general concerns as follows that are required to be addressed:

In Paragraph 3 of section 2 we dive into VE of a bunch of vaccines without any real understanding of what vaccine is what.  It would be beneficial to have a paragraph on the different types of vaccines or at least demarcate the VE of the different types rather than lump them in together. Also the RNA vaccines initially had a very high VE >90% with the original strain. This review jumps straight into the VE with the Omicron variant. A review should review.

“. Another strategy is to include more key epitopes of SARS-CoV-2 or even epitopes of other coronaviruses in the next generation vaccine design, in order to increase the chance of generating more cross-protective antibodies to deal with new mutations of the virus” – requires further expansion. It should be pointed out to the reader that while this is ideal regulatory authorities require that the components of a vaccine must be clinically relevant. For this reason, we do not have a pandemic influenza strain in the current seasonal vaccine. Further what antigen would they suggest? Perhaps referencing the discussion below in their review?

In Section 3: Live attenuated approaches and the question of life long immunity. The authors have not really thought this through. We do not understand what induces life long immunity. To date the only examples are with vaccines directed to DNA viruses with the exception of measles. These DNA viruses do not vary their genomes and thus have poor ability to escape.  Measles has evolved to the point that it has an R0 of 20 and thus any variant that arises during an infection has to compete with a virus that is perhaps the most well adapted it can be to its receptor and thus does not have the opportunity to replicate.

“important genes in the virus's genetic sequence have been constantly changing ” is incorrect – the spike gene has only significantly changed

No discussion of immune imprinting. This should be added since it is a significant issue.

There are a significant number of grammatical errors and typos:

Grammar:

Line 48: at which the virus is mutating the neutralizing epitopes

Line 49: symptomatic treatments are widely followed in clinical therapeutics

Line 64: is a gradual increase in the number of mutation sites

Line 79: From the late 2021

Line 84: the orange 84 curve, which represents the number of deaths, has been gradually declining should read : the number of deaths (the orange curve: Fig 2A), has been gradually declining

Line 90: ³¹ (the chart data source is the WHO) – unnecessary to double quote

Line 102/143: basal immunization – what does this mean?

Line 118: cross-antibodies should read cross reactive antibodies

Line 123: proven safe viral vectors

Line 124; proven lifetime immunity

Line 140: the novel coronavirus variant

Line 197: mix a certain percentage of mRNA
line 309: especially to elder population.

Line 310: . It's even better if there are therapeutic effects

Typos:

Line 86: than15‰

Line 86/87: (Jun,2021 86 to Dec,2021)

Line 87 5‰

Line 153: postvaccination

Line 310 no full stop

Author Response

The authors compile a more recent review of current and potential vaccines for COVID-19 and sarbecoviruses.  This review would be significantly improved by stating that the review will concentrate on the appearance of the VoC Omicron strain to alert the reader that this is the focus of the review. If not a significant amount of work is required to edit this review. I have some general concerns as follows that are required to be addressed:

1. In Paragraph 3 of section 2 we dive into VE of a bunch of vaccines without any real understanding of what vaccine is what.  It would be beneficial to have a paragraph on the different types of vaccines or at least demarcate the VE of the different types rather than lump them in together. Also the RNA vaccines initially had a very high VE >90% with the original strain. This review jumps straight into the VE with the Omicron variant. A review should review.

2. Another strategy is to include more key epitopes of SARS-CoV-2 or even epitopes of other coronaviruses in the next generation vaccine design, in order to increase the chance of generating more cross-protective antibodies to deal with new mutations of the virus” – requires further expansion. It should be pointed out to the reader that while this is ideal regulatory authorities require that the components of a vaccine must be clinically relevant. For this reason, we do not have a pandemic influenza strain in the current seasonal vaccine. Further what antigen would they suggest? Perhaps referencing the discussion below in their review?

The discussion of this part is added in lines 182-188

3. In Section 3: Live attenuated approaches and the question of life long immunity. The authors have not really thought this through. We do not understand what induces life long immunity. To date the only examples are with vaccines directed to DNA viruses with the exception of measles. These DNA viruses do not vary their genomes and thus have poor ability to escape.  Measles has evolved to the point that it has an R0 of 20 and thus any variant that arises during an infection has to compete with a virus that is perhaps the most well adapted it can be to its receptor and thus does not have the opportunity to replicate.

The section on lifelong immunity was deleted

4. “important genes in the virus's genetic sequence have been constantly changing ” is incorrect – the spike gene has only significantly changed

This sentence was amended: During the three years of the coronavirus epidemic, Viruses evolve as they spread.

5. No discussion of immune imprinting. This should be added since it is a significant issue.

The discussion about immune imprinting is added at the end of the text

There are a significant number of grammatical errors and typos:

These errors were corrected

Round 2

Reviewer 2 Report

This manuscript is improved form the first version and i support its publication